During malaria infection,elevated levels of pro-inflammatory mediators and nitric;oxide production have been associated with pathogenesis and disease severity.Previous in vitro and in vivo studies have proposed that b...During malaria infection,elevated levels of pro-inflammatory mediators and nitric;oxide production have been associated with pathogenesis and disease severity.Previous in vitro and in vivo studies have proposed that both Plasmodium falciparum hemozoin and glycosylphosphatidylinositols are able to modulate blood mononuclear cells,contributing to stimulation of signal transduction and downstream regulation of the NF-KB signaling pathway,and subsequently leading to the production of pro-inflammatory cytokines,chemokines,and nitric oxide.The present review summarizes the published in vitro and in vivo studies that have investigated the mechanism of intracellular signal transduction and activation of the NF-KB signaling pathway in blood mononuclear cells after being inducted by Plasmodium falciparum malaria components.Particular attention is paid to hemozoin and glycosylphosphatidylinositols which reflect the important mechanism of signaling pathways involved in immune response.展开更多
Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system(TCS), where they exhibit morphostatic function by stimula...Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system(TCS), where they exhibit morphostatic function by stimulatingproliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system(IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage Ⅳ ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.展开更多
目的研究NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示NLRP3炎性小体在慢阻肺发病机制中的可能作用。方法选取2016年11月至2017年5月住院的40例慢阻...目的研究NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示NLRP3炎性小体在慢阻肺发病机制中的可能作用。方法选取2016年11月至2017年5月住院的40例慢阻肺患者纳入急性加重期组,其经过治疗进入稳定期后纳入稳定期组,选取40例健康体检者纳入对照组。采集各组一般资料和外周血,荧光定量PCR法测定外周血单个核细胞中NLRP3 m RNA水平,酶联免疫法检测血浆白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)水平。结果急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于稳定期组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml,P<0.05]。急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。稳定期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。急性加重期组血浆IL-18水平和白细胞计数、中性粒细胞百分比呈正相关(r=0.372,P<0.05;r=0.386,P<0.05);急性加重期组NLRP3 m RNA表达量和稳定期组NLRP3 m RNA表达量均与CAT评分正相关(r=0.387,P<0.05;r=0.399,P<0.05)。结论 NLRP3炎性小体参与慢阻肺患者的机体炎症反应。展开更多
AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood m...AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.展开更多
Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the denta...Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.展开更多
BACKGROUND: Interleukin-18 (IL-18), a pro-inflamma- tory cytokine that induces interferon-γ (IFN-γ) production in T cells and natural killer cells, plays a critical role in the T-lymphocyte helper type 1 ( Th1) resp...BACKGROUND: Interleukin-18 (IL-18), a pro-inflamma- tory cytokine that induces interferon-γ (IFN-γ) production in T cells and natural killer cells, plays a critical role in the T-lymphocyte helper type 1 ( Th1) response. This study was designed to explore the effect of IL-18 on peripheral blood mononuclear cells ( PBMCs) derived from chronic hepatitis B (CHB) and on hepatitis B virus (HBV) DNA released by HepG2.2.15 cell lines, which were transfected with hepatitis B virus gene in vitro. METHODS: PBMCs isolated from 25 healthy people and 25 patients with CHB were stimulated with HBcAg and IL-18 of various concentrations for 72 hours. The levels of IFN-γ in the supernatants of cultured PBMCs were determined by ELISA. After the stimulation of IL-18 of various concentra- tions, PBMCs derived from one patient were co-cultured for 96 hours with HepG2. 2. 15 cells which had been cul- tured for 24 hours, and then the supernatants were collected by centrifugation and used for HBV DNA quantitative as- say. RESULTS: When PBMCs were stimulated by HBcAg and IL-18 at various concentrations, the levels of IFN-γ in the supernatants of CHB groups were much higher than those in normal control groups, at 0.2 ng/ml: t =11.70, P< 0.01; at 1.0 ng/ml: t =16.19, P<0.01; and at5.0 ng/ml: t =20.12, P <0.01. In the CHB groups, the levels of IFN-γ in the supernatants of PBMCs stimulated by HBcAg alone were lower than both those stimulated by HBcAg and EL-18 at various concentrations and those stimulated by HBcAg and EL-18 (5.0 ng/ml) together with EL-12 (mild: t = 2.20, P<0.05; moderate; t=2.97, P<0.05; severe; t = 0.66, P >0.05). The content of HBV DNA in the superna- tant of co-cultivation of HepG2. 2. 15 cells and PBMCs without stimulated materials was higher than that stimula-ted by HBcAg and EL-18 at various concentrations of HBc- Ag and IL-18 together with IL-12/IFN-α1lb. CONCLUSION: DL-18 can induce IFN-γ secretion and pro- bably play a key role in the modulation of both innate and adaptive immunity. It has implications in im展开更多
基金Supported by the Institute of Research and Development,Walailak University,Nakhon Si Thammarat,Thailand
文摘During malaria infection,elevated levels of pro-inflammatory mediators and nitric;oxide production have been associated with pathogenesis and disease severity.Previous in vitro and in vivo studies have proposed that both Plasmodium falciparum hemozoin and glycosylphosphatidylinositols are able to modulate blood mononuclear cells,contributing to stimulation of signal transduction and downstream regulation of the NF-KB signaling pathway,and subsequently leading to the production of pro-inflammatory cytokines,chemokines,and nitric oxide.The present review summarizes the published in vitro and in vivo studies that have investigated the mechanism of intracellular signal transduction and activation of the NF-KB signaling pathway in blood mononuclear cells after being inducted by Plasmodium falciparum malaria components.Particular attention is paid to hemozoin and glycosylphosphatidylinositols which reflect the important mechanism of signaling pathways involved in immune response.
文摘Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system(TCS), where they exhibit morphostatic function by stimulatingproliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system(IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage Ⅳ ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.
文摘目的研究NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示NLRP3炎性小体在慢阻肺发病机制中的可能作用。方法选取2016年11月至2017年5月住院的40例慢阻肺患者纳入急性加重期组,其经过治疗进入稳定期后纳入稳定期组,选取40例健康体检者纳入对照组。采集各组一般资料和外周血,荧光定量PCR法测定外周血单个核细胞中NLRP3 m RNA水平,酶联免疫法检测血浆白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)水平。结果急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于稳定期组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml,P<0.05]。急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。稳定期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。急性加重期组血浆IL-18水平和白细胞计数、中性粒细胞百分比呈正相关(r=0.372,P<0.05;r=0.386,P<0.05);急性加重期组NLRP3 m RNA表达量和稳定期组NLRP3 m RNA表达量均与CAT评分正相关(r=0.387,P<0.05;r=0.399,P<0.05)。结论 NLRP3炎性小体参与慢阻肺患者的机体炎症反应。
基金Supported by the Natural Science Foundation of Shandong Province,No.2014ZRB01466
文摘AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.
基金Supported by Austrian Science Fund,No.Project 29440(to Andrukhov O)
文摘Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability.Dental tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and gingiva.According to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell preparation.Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells.MSCs exert mostly immunosuppressive effects,leading to the dampening of immune cell activation.Thus,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression.Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability.Moreover,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity.MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues.Therefore,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.
文摘BACKGROUND: Interleukin-18 (IL-18), a pro-inflamma- tory cytokine that induces interferon-γ (IFN-γ) production in T cells and natural killer cells, plays a critical role in the T-lymphocyte helper type 1 ( Th1) response. This study was designed to explore the effect of IL-18 on peripheral blood mononuclear cells ( PBMCs) derived from chronic hepatitis B (CHB) and on hepatitis B virus (HBV) DNA released by HepG2.2.15 cell lines, which were transfected with hepatitis B virus gene in vitro. METHODS: PBMCs isolated from 25 healthy people and 25 patients with CHB were stimulated with HBcAg and IL-18 of various concentrations for 72 hours. The levels of IFN-γ in the supernatants of cultured PBMCs were determined by ELISA. After the stimulation of IL-18 of various concentra- tions, PBMCs derived from one patient were co-cultured for 96 hours with HepG2. 2. 15 cells which had been cul- tured for 24 hours, and then the supernatants were collected by centrifugation and used for HBV DNA quantitative as- say. RESULTS: When PBMCs were stimulated by HBcAg and IL-18 at various concentrations, the levels of IFN-γ in the supernatants of CHB groups were much higher than those in normal control groups, at 0.2 ng/ml: t =11.70, P< 0.01; at 1.0 ng/ml: t =16.19, P<0.01; and at5.0 ng/ml: t =20.12, P <0.01. In the CHB groups, the levels of IFN-γ in the supernatants of PBMCs stimulated by HBcAg alone were lower than both those stimulated by HBcAg and EL-18 at various concentrations and those stimulated by HBcAg and EL-18 (5.0 ng/ml) together with EL-12 (mild: t = 2.20, P<0.05; moderate; t=2.97, P<0.05; severe; t = 0.66, P >0.05). The content of HBV DNA in the superna- tant of co-cultivation of HepG2. 2. 15 cells and PBMCs without stimulated materials was higher than that stimula-ted by HBcAg and EL-18 at various concentrations of HBc- Ag and IL-18 together with IL-12/IFN-α1lb. CONCLUSION: DL-18 can induce IFN-γ secretion and pro- bably play a key role in the modulation of both innate and adaptive immunity. It has implications in im
