AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients...AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups:sulfasalazine group,who received sulfasalazine 2400 mg/d;and probiotic group,who received sulfasalazine 2400 mg/d with probiotic.The patients were investigated before and after 8 wk of treatment with probiotic(Lactobacillus delbruekii and Lactobacillus fermentum).Colonic activity of myeloperoxidase(MPO)was assayed with UV spectrophotometry,the colonic content of interleukin(IL)-6 was determined by enzyme-linked immunosorbent assay(ELISA),fecal calprotectin was determined by ELISA,and expression of NF-κB p65 and tumor necrosis factor (TNF)-αproteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction,respectively.RESULTS:At the start of the study,colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining,and an increase in colonic MPO activity,fecal calprotectin,and expression of colonic TNF-αand NF-κB p65 proteins.The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6,expression of TNF-αand NF-κB p65,leukocyte recruitment,as demonstrated by a decrease in colonic MPO activity,and the level of fecal calprotectin compared to sulfasalazine group and the control group(P<0.05).CONCLUSION:Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.展开更多
Background Experimental autoimmune myocarditis （EAM） in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a...Background Experimental autoimmune myocarditis （EAM） in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells （iDCs） ameliorate EAM and to explore the underlying mechanisms. Methods EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells （BMDCs） were generated without or with the stimulation by lipopolysaccharide （LPS） and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2× 10^6/per rat mature DC （mDC）, immature DC （iDC）, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline （PBS） were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IκB, the inhibitor of NF-κB pathway, was determined by Western blot. Results BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor （GM-CSF） were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature （m）DCs with higher levels of surface major histocompatibility complex （MHC）-Ⅱ and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent matu展开更多
Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 （IL-1） is not exp...Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 （IL-1） is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type Ⅱ. Methods Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type Ⅱ expression during treatment with IL-1, with or without the nuclear factor-κB （NF-κB） activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting, and the activity of the NF-κB signaling pathway was detected by the electrophoretic mobility shift assay （EMSA）. Results IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type Ⅱ in the cultured intervertebral disc cells in a dose dependent manner （P 〈0.05）, and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type Ⅱ expression （P 〉0.05）. IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-κB in the intervertebral disc cells in a dose dependent manner （P 〈0.05） that was inhibited by curcumin. Conclusions We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type Ⅱ via NF-κB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-κB activity inhibitor.展开更多
Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-...Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-kappa B （NF-kB） pathways in psoriasis vulgaris skin lesions. The expression levels of IL-36a, IL-3613, IL-367, phosphorylated p38 MAPK, and NF-id3p65 were detected in the skin tissues of 38 psoriasis patients and 17 healthy control subjects by real-time quantitative reverse transcription po lymerase chain reaction （qRT-PCR） and Western blotting. The cytokine expression levels were com pared between the psoriasis group and the control group. A correlation analysis between cytokine pro teins was performed in the psoriasis group. Results showed that the expression levels of IL-36a, IL-3613, IL-36y, phosphorylated p38 MAPK and NF-rh3p65 in the psoriasis group were Significantly higher than those in the control group （P〈0.001）. In the psoriasis group, the IL-36 cytokine expression was positively correlated with phosphorylated p38 MAPK and NF-kBp65 expression （P〈0.05）. A significant positive correlation was also found between the phosphorylated p38 MAPK and NF-v,.Bp65 expression （P〈0.01）. It was concluded that the increased IL-36 expression is correlated with p38 MAPK and NF-kB pathways in psoriasis vulgaris skin lesions. All the three factors may be jointly involved in the pathogenesis and local inflammatory response of psoriasis.展开更多
Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity,which is closely associated with inflammation.Benzydamine(BA)has been used as a cytokine-suppressive or non-steroidal...Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity,which is closely associated with inflammation.Benzydamine(BA)has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of proinflammatory cytokines or prostaglandins.However,its role in osteoclast differentiation and function remains unknown.Here,we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism.BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β(IL-1β)production.BA inhibited osteoclast formation and bone resorption when added to bone marrowderived macrophages and differentiated osteoclasts,and the inhibitory effect was reversed by IL-1βtreatment.The reporter assay and the inhibitor study of IL-1βtranscription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase,extracellular signal regulated kinase and P38,resulting in the down-regulation of IL-1βexpression.BA also promoted osteoblast differentiation.Furthermore,BA protected lipopolysaccharide-and ovariectomy-induced bone loss in mice,suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.展开更多
Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke an...Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.展开更多
Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in ...Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in which the tumor originates(e.g.,fibroblasts and endothelial cells)or those recruited,through chemotactic or other factors,to the tumor(e.g.,circulating immune cells).Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor.Immune cells can have both anti-tumor and pro-tumor activity.In addition,crosstalk between prostate cancer cells and immune cells affects immune cell functions.In this review,we focus on immune cells and cytokines that contribute to tumor progression.We discuss T-regulatory and T helper17 cells and macrophages as key modulators in prostate cancer progression.In addition,we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression.This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.展开更多
Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced...Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced by dextran sulfate sodium(DSS),and mice were divided into 4 groups:control.DSS alone.DSS plus SASP,DSS plus pectic polysaccharides.The disease activity index(DAI) and histological score were observed.The tumor necrosis factor(TNF)-α and interleukin(IL)-17 levels were measured by enzyme-linked immunosorbent assay.I κ B and NF-κB p65 expression were assessed by western blot analysis.Myeloperoxidase(MPO) activity was determined by using MPO assay kit.Re.sults:Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAT and histological score,and resulted in down regulation of MPO activity and NF-κB p65 expression and subsequent degradation of IκB protein,strikingly reduced the production of TNF-α and IL-17.Conclusions:Pectic polysaccharides extracted from Rauvolfia verticillata(Lour.)Baill.var.hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.展开更多
Injury of the periodontium followed by inflammatory response often leads to mot resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact ...Injury of the periodontium followed by inflammatory response often leads to mot resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact with the root, the cementoblasts. Our study aimed to investigate the role of human cementoblasts in the formation of osteoclasts and the effect of interleukin （IL）- 1β hereupon. Extracted teeth from healthy volunteers were subjected to sequential digestion by type I collagenase and trypsin. The effect of enzymatic digestion on the presence of cells on the root surface was analyzed by histology. Gene expression of primary human cementoblasts （pHCB） was compared with a human cementoblast cell line （HCEM）. The pHCBs were analyzed for their expression of IL-1 receptors as well as of receptor activator of nuclear factor kappa-B ligand （RANKL） and osteoprotegerin （OPG）. In a co-culture system consisting of osteoclast precursors （blood monocytes） and pHCBs, the formation of osteoclasts and their resorptive activity was assessed by osteo-assay and ivory slices. The cells obtained after a 120 min enzyme digestion expressed the highest level of bone sialoprotein, similar to that of HCEM. This fraction of isolated cells also shared a similar expression pattern of IL-1 receptors （ILl-R1 and ILl-R2）. Treatment with IL-11~ potently upregulated RANKL expression but not of OPG. pHCBs were shown to induce the formation of functional osteoclasts. This capacity was significantly stimulated by pretreating the pHCBs with IL-1β prior to their co-culture with human blood monocytes. Our study demonstrated that cementoblasts have the capacity to induce osteoclastogenesis, a capacity strongly promoted by IL-1β. These results may explain why osteoclasts can be formed next to the root of teeth.展开更多
Effect of interleukin-6 receptor （IL-6R） antibody on polymethyl methacrylate （PMMA） bone cement-mediated expression of osteoprotegerin （OPG） and ：receptor activator of nuclear fac- tor-kappaB ligand （RANKL） i...Effect of interleukin-6 receptor （IL-6R） antibody on polymethyl methacrylate （PMMA） bone cement-mediated expression of osteoprotegerin （OPG） and ：receptor activator of nuclear fac- tor-kappaB ligand （RANKL） in synovial fibroblasts was investigated. Synovial tissue obtained from to- tal knee arthroplasty was digested and cultured. Inverted microscope was employed to observe the synovial cells and immunocytochemistry （SABC method） staining was used to identify synovial fibro- blasts. This experiment was divided into three groups according to different culture media： PMMA group （75μg/mL PMMA bone cement particles）, IL-6R antibody group （10 ng/mL IL-6R antibody＋75 μg/mL PMMA bone cement particles）, and control group （no IL-6R antibody or PMMA bone cement particles）. Influence of IL-6R antibody and PMMA on proliferation of synovial fibroblasts was meas- ured by cell counting kit-8 （CCK-8）. ELISA method was used to measure OPG and RANKL levels in culture solution. Fluorescence quantitative real-time PCR （FQ-PCR） was used to detect the expression of OPG and RANKL mRNA. After three consecutive passages, more than 95% of the primary synovial cells became long spindle fibroblast-like cells. SABC staining results showed that the fibroblast-like cells were negative for anti-CD68 antibody and positive for anti-vimentin antibody, with brown madder stained. CCK-8 test demonstrated that the absorbance （A） value at 450 nm was significantly lower in IL-6R antibody group than in PMMA group and control group （P〈0.01）, but there was no statistically significant difference in A value at 450 nm between the control group and PMMA group （P〉0.05）. Re- suits of ELISA indicated that the expression of OPG was significantly higher in IL-6R antibody group than in PMMA group and control group （P〈0.01）. The expression of RANKL was inhibited （P〈0.05）, and the ratio of OPG/RANKL was significantly increased in IL-6R antibody group as compared with PMMA group and control gro展开更多
BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expressi...BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B （ kB）, interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia. DESIGN, TIME AND SETTING： The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIALS： A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320g, were selected. Naoxintong powder （mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis） was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608. METHODS： The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 g/kg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage All rats were administered by gavage at 5 and 23 hours following surgery, and subsequently, once per day. MAIN OUTCOME MEASURES： At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor- α, and complement 3 was examined by immunohistochemistry. RESULTS： A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as well as the high-dose, mo展开更多
Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Berberine, the effective ingredient of Coptidis Rhizoma and Cortex Phellodendti...Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Berberine, the effective ingredient of Coptidis Rhizoma and Cortex Phellodendti, has a wide range of pharmacological functions, including anti-inflammatory, anti-atherosclerotic and anti-cancer effects. The neuroprotective potential of berberine has previously been demonstrated. The present study aimed to examine whether berberine could repress microglial activation and can be considered a potential therapeutic candidate to target neurodegenerative diseases. Primary microglial cells and BV2 microglial cells were cultured and stimulated with bacterial lipopolysaccharide （LPS）. Berberine chloride was treated prior to LPS or simultaneously with LPS stimulation. Results revealed that berberine was effective at inhibiting nitric oxide release from primary microglial cells when cells were exposed to the compound prior to LPS or simultaneously with LPS. It also reduced the LPS-stimulated production of tumor necrosis factor-α, interleukin-1β, prostaglandin E2, and intracellular reactive oxygen species and nuclear factor-kappa activation. Additionally, berberine reduced nitric oxide release from microglia stimulated with interferon-γ and amyloid β. These results suggest that berberine provides neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.展开更多
Background:Inflammation is an important factor in pathological scarring.The role of neutrophils,one of the most important inflammatory cells,in scar hyperplasia remains unclear.The purpose of this article is to study ...Background:Inflammation is an important factor in pathological scarring.The role of neutrophils,one of the most important inflammatory cells,in scar hyperplasia remains unclear.The purpose of this article is to study the correlation between neutrophil extracellular traps(NETs)and scar hyperplasia and identify a new target for inhibiting scar hyperplasia.Methods:Neutrophils were isolated from human peripheral blood by magnetic-bead sorting.NETs in plasma and scars were detected by enzyme-linked immunosorbent assays(ELISAs),immunofluorescence and flow cytometry.Immunohistochemistry was used to assess neutrophil(CD66B)infiltration in hypertrophic scars.To observe the entry of NETs into fibroblasts we used immunofluorescence and flow cytometry.Results:We found that peripheral blood neutrophils in patients with hypertrophic scars were more likely to form NETs(p<0.05).Hypertrophic scars showed greater infiltration with neutrophils and NETs(p<0.05).NETs activate fibroblasts in vitro to promote their differentiation and migration.Inhibition of NETs with cytochalasin in wounds reduced the hyperplasia of scars in mice.We induced neutrophils to generate NETs with different stimuli in vitro and detected the proteins carried by NETs.We did not find an increase in the expression of common scarring factors[interleukin(IL)-17 and transforming growth factor-β(TGF-β),p>0.05].However,inhibiting the production of NETs or degrading DNA reduced the differentiation of fibroblasts intomyofibroblasts.In vitro,NETs were found to be mediated by Toll-like receptor 9(TLR-9)in fibroblasts and further phosphorylated nuclear factor Kappa-B(NF-κB).We found that IL-6,which is downstream of NF-κB,was increased in fibroblasts.Additionally,IL-6 uses autocrine and paracrine signaling to promote differentiation and secretion.Conclusions:Our experiments found that NETs activate fibroblasts through the TLR-9/NF-κB/IL-6 pathway,thereby providing a new target for regulating hypertrophic scars.展开更多
文摘AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups:sulfasalazine group,who received sulfasalazine 2400 mg/d;and probiotic group,who received sulfasalazine 2400 mg/d with probiotic.The patients were investigated before and after 8 wk of treatment with probiotic(Lactobacillus delbruekii and Lactobacillus fermentum).Colonic activity of myeloperoxidase(MPO)was assayed with UV spectrophotometry,the colonic content of interleukin(IL)-6 was determined by enzyme-linked immunosorbent assay(ELISA),fecal calprotectin was determined by ELISA,and expression of NF-κB p65 and tumor necrosis factor (TNF)-αproteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction,respectively.RESULTS:At the start of the study,colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining,and an increase in colonic MPO activity,fecal calprotectin,and expression of colonic TNF-αand NF-κB p65 proteins.The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6,expression of TNF-αand NF-κB p65,leukocyte recruitment,as demonstrated by a decrease in colonic MPO activity,and the level of fecal calprotectin compared to sulfasalazine group and the control group(P<0.05).CONCLUSION:Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.
基金This study was supported by Harbin Medical University Postgraduate Creation Foundation (2005).
文摘Background Experimental autoimmune myocarditis （EAM） in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells （iDCs） ameliorate EAM and to explore the underlying mechanisms. Methods EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells （BMDCs） were generated without or with the stimulation by lipopolysaccharide （LPS） and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2× 10^6/per rat mature DC （mDC）, immature DC （iDC）, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline （PBS） were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IκB, the inhibitor of NF-κB pathway, was determined by Western blot. Results BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor （GM-CSF） were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature （m）DCs with higher levels of surface major histocompatibility complex （MHC）-Ⅱ and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent matu
基金The study was supported by a grant from the National Natural Science Foundation of China （No. 2004NSFC30471741）.
文摘Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 （IL-1） is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type Ⅱ. Methods Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type Ⅱ expression during treatment with IL-1, with or without the nuclear factor-κB （NF-κB） activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting, and the activity of the NF-κB signaling pathway was detected by the electrophoretic mobility shift assay （EMSA）. Results IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type Ⅱ in the cultured intervertebral disc cells in a dose dependent manner （P 〈0.05）, and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type Ⅱ expression （P 〉0.05）. IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-κB in the intervertebral disc cells in a dose dependent manner （P 〈0.05） that was inhibited by curcumin. Conclusions We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type Ⅱ via NF-κB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-κB activity inhibitor.
基金supported by grants from the National Natural Science Foundation of China(No.30972654,No.81101191,No.81271765 and No.81171495)
文摘Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-kappa B （NF-kB） pathways in psoriasis vulgaris skin lesions. The expression levels of IL-36a, IL-3613, IL-367, phosphorylated p38 MAPK, and NF-id3p65 were detected in the skin tissues of 38 psoriasis patients and 17 healthy control subjects by real-time quantitative reverse transcription po lymerase chain reaction （qRT-PCR） and Western blotting. The cytokine expression levels were com pared between the psoriasis group and the control group. A correlation analysis between cytokine pro teins was performed in the psoriasis group. Results showed that the expression levels of IL-36a, IL-3613, IL-36y, phosphorylated p38 MAPK and NF-rh3p65 in the psoriasis group were Significantly higher than those in the control group （P〈0.001）. In the psoriasis group, the IL-36 cytokine expression was positively correlated with phosphorylated p38 MAPK and NF-kBp65 expression （P〈0.05）. A significant positive correlation was also found between the phosphorylated p38 MAPK and NF-v,.Bp65 expression （P〈0.01）. It was concluded that the increased IL-36 expression is correlated with p38 MAPK and NF-kB pathways in psoriasis vulgaris skin lesions. All the three factors may be jointly involved in the pathogenesis and local inflammatory response of psoriasis.
基金supported by the National Research Foundation(NRF)(Grant Nos.2017R1A2B2012435,2019R1C1C1011198 and 2019R1A5A6099645,Korea)funded by the Korean Ministry of Science,ICT and future Planning(MSIP).
文摘Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity,which is closely associated with inflammation.Benzydamine(BA)has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of proinflammatory cytokines or prostaglandins.However,its role in osteoclast differentiation and function remains unknown.Here,we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism.BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β(IL-1β)production.BA inhibited osteoclast formation and bone resorption when added to bone marrowderived macrophages and differentiated osteoclasts,and the inhibitory effect was reversed by IL-1βtreatment.The reporter assay and the inhibitor study of IL-1βtranscription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase,extracellular signal regulated kinase and P38,resulting in the down-regulation of IL-1βexpression.BA also promoted osteoblast differentiation.Furthermore,BA protected lipopolysaccharide-and ovariectomy-induced bone loss in mice,suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.
基金founded by JSPS KAKENHI,No.24390416,JP15H05015,15K15684 and JP16H01304(all to HN)
文摘Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging.
基金supported by National Cancer Institute Grants(Nos.P01 CA093900 and R01 CA190554)National Natural Science Foundation of China(NSFC)Key Projects(Nos.81130046+1 种基金NSFC 81171993 and 81272415)Guangxi Key Project(No.2013GXNSFEA053004)
文摘Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in which the tumor originates(e.g.,fibroblasts and endothelial cells)or those recruited,through chemotactic or other factors,to the tumor(e.g.,circulating immune cells).Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor.Immune cells can have both anti-tumor and pro-tumor activity.In addition,crosstalk between prostate cancer cells and immune cells affects immune cell functions.In this review,we focus on immune cells and cytokines that contribute to tumor progression.We discuss T-regulatory and T helper17 cells and macrophages as key modulators in prostate cancer progression.In addition,we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression.This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.
基金supported by National Natural Science Foundation of China(Grant No.81360603)Natural Science Foundation of Hainan Province(Grant No.813215)
文摘Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced by dextran sulfate sodium(DSS),and mice were divided into 4 groups:control.DSS alone.DSS plus SASP,DSS plus pectic polysaccharides.The disease activity index(DAI) and histological score were observed.The tumor necrosis factor(TNF)-α and interleukin(IL)-17 levels were measured by enzyme-linked immunosorbent assay.I κ B and NF-κB p65 expression were assessed by western blot analysis.Myeloperoxidase(MPO) activity was determined by using MPO assay kit.Re.sults:Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAT and histological score,and resulted in down regulation of MPO activity and NF-κB p65 expression and subsequent degradation of IκB protein,strikingly reduced the production of TNF-α and IL-17.Conclusions:Pectic polysaccharides extracted from Rauvolfia verticillata(Lour.)Baill.var.hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.
基金Ratchadaphiseksomphot Endowment Fund Chulalongkorn University(R/F_2557_021_03_32)Integrated-Innovation Academic Center’Chulalongkorn University Centenary Academic Development Project+1 种基金The 2012 Research Chair GrantThailand National Science and Technology Development Agency(NSTDA)
文摘Injury of the periodontium followed by inflammatory response often leads to mot resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact with the root, the cementoblasts. Our study aimed to investigate the role of human cementoblasts in the formation of osteoclasts and the effect of interleukin （IL）- 1β hereupon. Extracted teeth from healthy volunteers were subjected to sequential digestion by type I collagenase and trypsin. The effect of enzymatic digestion on the presence of cells on the root surface was analyzed by histology. Gene expression of primary human cementoblasts （pHCB） was compared with a human cementoblast cell line （HCEM）. The pHCBs were analyzed for their expression of IL-1 receptors as well as of receptor activator of nuclear factor kappa-B ligand （RANKL） and osteoprotegerin （OPG）. In a co-culture system consisting of osteoclast precursors （blood monocytes） and pHCBs, the formation of osteoclasts and their resorptive activity was assessed by osteo-assay and ivory slices. The cells obtained after a 120 min enzyme digestion expressed the highest level of bone sialoprotein, similar to that of HCEM. This fraction of isolated cells also shared a similar expression pattern of IL-1 receptors （ILl-R1 and ILl-R2）. Treatment with IL-11~ potently upregulated RANKL expression but not of OPG. pHCBs were shown to induce the formation of functional osteoclasts. This capacity was significantly stimulated by pretreating the pHCBs with IL-1β prior to their co-culture with human blood monocytes. Our study demonstrated that cementoblasts have the capacity to induce osteoclastogenesis, a capacity strongly promoted by IL-1β. These results may explain why osteoclasts can be formed next to the root of teeth.
基金supported by grants from the Research and Development Projects of Shenzhen of P.R.China(No.JCYJ20130402114702130)the Healthcare and Medical Research Fund of Shenzhen of P.R.China(No.201302064)
文摘Effect of interleukin-6 receptor （IL-6R） antibody on polymethyl methacrylate （PMMA） bone cement-mediated expression of osteoprotegerin （OPG） and ：receptor activator of nuclear fac- tor-kappaB ligand （RANKL） in synovial fibroblasts was investigated. Synovial tissue obtained from to- tal knee arthroplasty was digested and cultured. Inverted microscope was employed to observe the synovial cells and immunocytochemistry （SABC method） staining was used to identify synovial fibro- blasts. This experiment was divided into three groups according to different culture media： PMMA group （75μg/mL PMMA bone cement particles）, IL-6R antibody group （10 ng/mL IL-6R antibody＋75 μg/mL PMMA bone cement particles）, and control group （no IL-6R antibody or PMMA bone cement particles）. Influence of IL-6R antibody and PMMA on proliferation of synovial fibroblasts was meas- ured by cell counting kit-8 （CCK-8）. ELISA method was used to measure OPG and RANKL levels in culture solution. Fluorescence quantitative real-time PCR （FQ-PCR） was used to detect the expression of OPG and RANKL mRNA. After three consecutive passages, more than 95% of the primary synovial cells became long spindle fibroblast-like cells. SABC staining results showed that the fibroblast-like cells were negative for anti-CD68 antibody and positive for anti-vimentin antibody, with brown madder stained. CCK-8 test demonstrated that the absorbance （A） value at 450 nm was significantly lower in IL-6R antibody group than in PMMA group and control group （P〈0.01）, but there was no statistically significant difference in A value at 450 nm between the control group and PMMA group （P〉0.05）. Re- suits of ELISA indicated that the expression of OPG was significantly higher in IL-6R antibody group than in PMMA group and control group （P〈0.01）. The expression of RANKL was inhibited （P〈0.05）, and the ratio of OPG/RANKL was significantly increased in IL-6R antibody group as compared with PMMA group and control gro
基金Supported by: the Scientific Technology Research and Development Plan of Hebei Province, No. 06276103Dthe Natural Science Foundation of Hebei Province, No. C2006000915
文摘BACKGROUND： Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury. OBJECTIVE： To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B （ kB）, interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia. DESIGN, TIME AND SETTING： The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIALS： A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320g, were selected. Naoxintong powder （mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis） was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608. METHODS： The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 g/kg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage All rats were administered by gavage at 5 and 23 hours following surgery, and subsequently, once per day. MAIN OUTCOME MEASURES： At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- kB, interleukin-6, tumor necrosis factor- α, and complement 3 was examined by immunohistochemistry. RESULTS： A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as well as the high-dose, mo
基金the Program of Kyung Hee University for Young Researchers in Medical Science,No.KHU-20081253
文摘Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Berberine, the effective ingredient of Coptidis Rhizoma and Cortex Phellodendti, has a wide range of pharmacological functions, including anti-inflammatory, anti-atherosclerotic and anti-cancer effects. The neuroprotective potential of berberine has previously been demonstrated. The present study aimed to examine whether berberine could repress microglial activation and can be considered a potential therapeutic candidate to target neurodegenerative diseases. Primary microglial cells and BV2 microglial cells were cultured and stimulated with bacterial lipopolysaccharide （LPS）. Berberine chloride was treated prior to LPS or simultaneously with LPS stimulation. Results revealed that berberine was effective at inhibiting nitric oxide release from primary microglial cells when cells were exposed to the compound prior to LPS or simultaneously with LPS. It also reduced the LPS-stimulated production of tumor necrosis factor-α, interleukin-1β, prostaglandin E2, and intracellular reactive oxygen species and nuclear factor-kappa activation. Additionally, berberine reduced nitric oxide release from microglia stimulated with interferon-γ and amyloid β. These results suggest that berberine provides neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.
基金supported by the National Natural Science Foundation of China,(No.82072217,81772135 and U21A20370)by the Jiangsu Natural Science Foundation(No.BK20201178).
文摘Background:Inflammation is an important factor in pathological scarring.The role of neutrophils,one of the most important inflammatory cells,in scar hyperplasia remains unclear.The purpose of this article is to study the correlation between neutrophil extracellular traps(NETs)and scar hyperplasia and identify a new target for inhibiting scar hyperplasia.Methods:Neutrophils were isolated from human peripheral blood by magnetic-bead sorting.NETs in plasma and scars were detected by enzyme-linked immunosorbent assays(ELISAs),immunofluorescence and flow cytometry.Immunohistochemistry was used to assess neutrophil(CD66B)infiltration in hypertrophic scars.To observe the entry of NETs into fibroblasts we used immunofluorescence and flow cytometry.Results:We found that peripheral blood neutrophils in patients with hypertrophic scars were more likely to form NETs(p<0.05).Hypertrophic scars showed greater infiltration with neutrophils and NETs(p<0.05).NETs activate fibroblasts in vitro to promote their differentiation and migration.Inhibition of NETs with cytochalasin in wounds reduced the hyperplasia of scars in mice.We induced neutrophils to generate NETs with different stimuli in vitro and detected the proteins carried by NETs.We did not find an increase in the expression of common scarring factors[interleukin(IL)-17 and transforming growth factor-β(TGF-β),p>0.05].However,inhibiting the production of NETs or degrading DNA reduced the differentiation of fibroblasts intomyofibroblasts.In vitro,NETs were found to be mediated by Toll-like receptor 9(TLR-9)in fibroblasts and further phosphorylated nuclear factor Kappa-B(NF-κB).We found that IL-6,which is downstream of NF-κB,was increased in fibroblasts.Additionally,IL-6 uses autocrine and paracrine signaling to promote differentiation and secretion.Conclusions:Our experiments found that NETs activate fibroblasts through the TLR-9/NF-κB/IL-6 pathway,thereby providing a new target for regulating hypertrophic scars.
