The high mobility group box 1(HMGB1),which belongs to the subfamily of HMG-1/-2,is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da.HMGB1 ...The high mobility group box 1(HMGB1),which belongs to the subfamily of HMG-1/-2,is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da.HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases.Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis.Acute pancreatitis is an acute inflammatory process of the pancreas(duration of less than six months),for which the severe form is called severe acute pancreatitis(SAP).More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP.Extracellular HMGB1 can aggravate the pancreatic inflammatory process,whereas intracellular HMGB1 has a protective effect against pancreatitis.The mechanism of HMGB1 is multiple,mainly through the nuclear factor-κB pathway.Receptors for advanced glycation endproducts and toll-like receptors(TLR),especially TLR-2 and TLR-4,are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP.HMGB1 inhibitors,such as ethyl pyruvate,pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans,can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP.展开更多
BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMG...BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken展开更多
目的探索早期肠内营养对肺癌患者肺部感染血清炎症因子与高迁移率族蛋白1(High Mobility Group Box-1protein,HMGB1)的临床影响。方法选取2014年1月-2017年1月于医院接受治疗的肺癌并发肺部感染患者288例为研究对象,按照是否接受早期肠...目的探索早期肠内营养对肺癌患者肺部感染血清炎症因子与高迁移率族蛋白1(High Mobility Group Box-1protein,HMGB1)的临床影响。方法选取2014年1月-2017年1月于医院接受治疗的肺癌并发肺部感染患者288例为研究对象,按照是否接受早期肠内营养分为营养组132例和对照组156例,对照组接受常规治疗,肠内营养组接受早期肠内营养治疗,比较两组患者血常规指标[包括:前白蛋白(PA)、血蛋白(ALB)、谷草转氨酶(AST)、尿素氮(BUN),肌酐(SCR)等]和HMGB1水平。结果治疗前两组患者PA、ALB、AST、BUN、SCR、C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)、白细胞介素-6(IL-6)HMGB1、CEA差异无统计学意义;治疗后营养组患者PA、ALB、AST和SCR分别为(228.43±21.55)g/L、(32.34±4.94)g/L、(41.38±7.04)IU/L和(83.44±12.18)μmol/L均高于对照组,BUN为(4.19±1.58)mmol/L低于对照组(P均<0.001)。治疗后营养组患者CRP、TNF-α、PCT、IL-6、分别为(33.72±12.55)g/L、(93.57±14.66)ng/ml、(6.13±4.68)ng/ml、(22.03±15.33)pg/ml低于对照组(P均<0.001)。治疗后营养组患者HMGB1、CEA分别为(8.03±2.06)ng/ml和(17.29±6.98)ng/ml高于对照组(P<0.001)。结论早期肠内营养能有效改善血清炎症因子水平,而血清HMGB1水平在肺癌合并肺部感染患者接受早期肠内营养中升高,可能在肺癌及肺部感染疾病发病机制中起重要作用,具有一定的临床意义。展开更多
High mobility group box 1 protein （HMGB1） is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory...High mobility group box 1 protein （HMGB1） is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. This systemic review is mainly based on our own work and other related reports HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells （Tregs）, dendritic cells （DCs）, macrophages, and natural killer cells （NK cells）. Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products （RAGE）, Toll-like receptor （TLR）2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors （e.g., ethyl pyruvate） and antagonists （e.g., A box）, can protect against sepsis lethality and give a wider window for the treatment opportunity. HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.展开更多
基金Supported by National Science Foundation of China,No.81170438grant from Jiangsu Provincial Special Program of Medical Science,No.BL2012006
文摘The high mobility group box 1(HMGB1),which belongs to the subfamily of HMG-1/-2,is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da.HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases.Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis.Acute pancreatitis is an acute inflammatory process of the pancreas(duration of less than six months),for which the severe form is called severe acute pancreatitis(SAP).More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP.Extracellular HMGB1 can aggravate the pancreatic inflammatory process,whereas intracellular HMGB1 has a protective effect against pancreatitis.The mechanism of HMGB1 is multiple,mainly through the nuclear factor-κB pathway.Receptors for advanced glycation endproducts and toll-like receptors(TLR),especially TLR-2 and TLR-4,are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP.HMGB1 inhibitors,such as ethyl pyruvate,pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans,can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP.
基金supported by a grant from the National Natural Science Foundation of China (No. 81071342)
文摘BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken
文摘目的探索早期肠内营养对肺癌患者肺部感染血清炎症因子与高迁移率族蛋白1(High Mobility Group Box-1protein,HMGB1)的临床影响。方法选取2014年1月-2017年1月于医院接受治疗的肺癌并发肺部感染患者288例为研究对象,按照是否接受早期肠内营养分为营养组132例和对照组156例,对照组接受常规治疗,肠内营养组接受早期肠内营养治疗,比较两组患者血常规指标[包括:前白蛋白(PA)、血蛋白(ALB)、谷草转氨酶(AST)、尿素氮(BUN),肌酐(SCR)等]和HMGB1水平。结果治疗前两组患者PA、ALB、AST、BUN、SCR、C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)、白细胞介素-6(IL-6)HMGB1、CEA差异无统计学意义;治疗后营养组患者PA、ALB、AST和SCR分别为(228.43±21.55)g/L、(32.34±4.94)g/L、(41.38±7.04)IU/L和(83.44±12.18)μmol/L均高于对照组,BUN为(4.19±1.58)mmol/L低于对照组(P均<0.001)。治疗后营养组患者CRP、TNF-α、PCT、IL-6、分别为(33.72±12.55)g/L、(93.57±14.66)ng/ml、(6.13±4.68)ng/ml、(22.03±15.33)pg/ml低于对照组(P均<0.001)。治疗后营养组患者HMGB1、CEA分别为(8.03±2.06)ng/ml和(17.29±6.98)ng/ml高于对照组(P<0.001)。结论早期肠内营养能有效改善血清炎症因子水平,而血清HMGB1水平在肺癌合并肺部感染患者接受早期肠内营养中升高,可能在肺癌及肺部感染疾病发病机制中起重要作用,具有一定的临床意义。
基金supported,in part,by grants from the National Natural Science Foundation(Nos.81130035,30901561,30971192,81071545)the National Basic Research Program of China(No.2012CB518102)the China Postdoctoral Science Foundation(Nos.20100480347,201104125)
文摘High mobility group box 1 protein （HMGB1） is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. This systemic review is mainly based on our own work and other related reports HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells （Tregs）, dendritic cells （DCs）, macrophages, and natural killer cells （NK cells）. Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products （RAGE）, Toll-like receptor （TLR）2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors （e.g., ethyl pyruvate） and antagonists （e.g., A box）, can protect against sepsis lethality and give a wider window for the treatment opportunity. HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.
