Interferon(IFN) with antiviral and im-munomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the ty...Interferon(IFN) with antiviral and im-munomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the types of IFN, which suppresses proliferation and induces apoptosis in some cell types while inhibiting apoptosis in others. The aim of this study was to explore the effect of IFNα-2a on Fas expression and the apoptosis rate of peripheral blood cytotoxic T cells (CTLs) in patients with hepatitis B. METHODS:Peripheral blood mononuclear cells were isolated from 26 patients with hepatitis B including 16 patients with chronic hepatitis B and 10 patients with chronic severe hepatitis B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry before and after IFNα-2a treatment. RESULTS:Before IFNα-2a treatment, Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B were significantly higher than those from patients with chronic severe hepatitis B and healthy controls respectively. No significant difference was observed between Fas expression and apoptosis rate of CTLs from patients with chronic severe hepatitis B and healthy controls. After IFNα-2a treatment,Fas expression and apoptosis rate of CTLs from different groups were compared with those before IFNα-2a treatment, showing no significant difference despite alternation of different degree. CONCLUSIONS:Activation induced cell death (AICD) exists in peripheral blood CTLs from patients with hepatitis B. No effect of IFNα-2a exerts on Fas expression and apoptosis rate of Fas in patients with hepatitis B.展开更多
The etiology and the underlying mechanism of CD4＋ T-cell polarization are unclear. This study sought to investigate the mechanism by which interleukin （IL）-13 prevents the activation-induced apoptosis of CD4＋ T ce...The etiology and the underlying mechanism of CD4＋ T-cell polarization are unclear. This study sought to investigate the mechanism by which interleukin （IL）-13 prevents the activation-induced apoptosis of CD4＋ T cells. Here we report that CD4＋ T cells expressed IL-13 receptor a2 in the intestine of sensitized mice. IL-13 suppressed both the activation-induced apoptosis of CD4＋ T cells and the expression of p53 and FasL. Exposure to recombinant IL-13 inhibited activation-induced cell death （AICD） along with the expression of p53, caspase 3, and tumor necrosis factor-a in CD4＋ T cells. Administration of an anti-lL-13 antibody enhanced the effect of specific immunotherapy on allergic inflammation in the mouse intestine, enforced the expression of p53 in intestinal CD4＋ T cells, and enhanced the frequency of CD4＋ T-cell apoptosis upon challenge with specific antigens. In summary, blocking IL-13 enhances the therapeutic effect of antigen-specific immunotheraov by regulating aDoptosis and thereby enforcing AICD in CD4＋ T cells.展开更多
In recent years, people have maked a great deal of investigation on and gained remarkable insight into the mechanism of chronicity of HBV infection, including: ①HBV antigenspecific cytotoxic T cells (CTL)undergo &quo...In recent years, people have maked a great deal of investigation on and gained remarkable insight into the mechanism of chronicity of HBV infection, including: ①HBV antigenspecific cytotoxic T cells (CTL)undergo "activation-induced cell death (AICD)"more severely than usual,so they can’t eradicate HBV infected target cells; ②these CTL can also damage other immune active cells and contribute to forming wide immunosupression in hosts；③the balance between Th1 and Th2 cells’ response may be disturbed； ④ gene mutation and/or expression deficiency of antiviral cytokines and their receptors have occurred；⑤antigen presenting cells(APC) process and present vira antigens deficiently; ⑥some circulating immune complexes (CIC) may contribute to chronicity of HBV infection； ⑦hepatocytes can’t execute fully their cooperative function in immune response and regulation； ⑧HBV-specific T cells have suffered clonal deletion during the ontogeny period;⑨ HBxAg can trans-activate the human multidrug resistance (MDR)-1 gene and associated genes;and ⑩mutation of viral genome and antigen have emerged under host’s immune pressure. In this review,we have discussed all these items and pointed out that there still have many other questions to be researched and clarified.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
文摘Interferon(IFN) with antiviral and im-munomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the types of IFN, which suppresses proliferation and induces apoptosis in some cell types while inhibiting apoptosis in others. The aim of this study was to explore the effect of IFNα-2a on Fas expression and the apoptosis rate of peripheral blood cytotoxic T cells (CTLs) in patients with hepatitis B. METHODS:Peripheral blood mononuclear cells were isolated from 26 patients with hepatitis B including 16 patients with chronic hepatitis B and 10 patients with chronic severe hepatitis B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry before and after IFNα-2a treatment. RESULTS:Before IFNα-2a treatment, Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B were significantly higher than those from patients with chronic severe hepatitis B and healthy controls respectively. No significant difference was observed between Fas expression and apoptosis rate of CTLs from patients with chronic severe hepatitis B and healthy controls. After IFNα-2a treatment,Fas expression and apoptosis rate of CTLs from different groups were compared with those before IFNα-2a treatment, showing no significant difference despite alternation of different degree. CONCLUSIONS:Activation induced cell death (AICD) exists in peripheral blood CTLs from patients with hepatitis B. No effect of IFNα-2a exerts on Fas expression and apoptosis rate of Fas in patients with hepatitis B.
文摘The etiology and the underlying mechanism of CD4＋ T-cell polarization are unclear. This study sought to investigate the mechanism by which interleukin （IL）-13 prevents the activation-induced apoptosis of CD4＋ T cells. Here we report that CD4＋ T cells expressed IL-13 receptor a2 in the intestine of sensitized mice. IL-13 suppressed both the activation-induced apoptosis of CD4＋ T cells and the expression of p53 and FasL. Exposure to recombinant IL-13 inhibited activation-induced cell death （AICD） along with the expression of p53, caspase 3, and tumor necrosis factor-a in CD4＋ T cells. Administration of an anti-lL-13 antibody enhanced the effect of specific immunotherapy on allergic inflammation in the mouse intestine, enforced the expression of p53 in intestinal CD4＋ T cells, and enhanced the frequency of CD4＋ T-cell apoptosis upon challenge with specific antigens. In summary, blocking IL-13 enhances the therapeutic effect of antigen-specific immunotheraov by regulating aDoptosis and thereby enforcing AICD in CD4＋ T cells.
基金Supported by National Natural Science Foundation of China(81601373)National Fund for Studying Abroad+2 种基金Hubei Youth Science and Technology Talent Development PlanXiangyang Youth Science and Technology Talent Development Plan(No.[2018]46)the Project for Discipline Groups Construction of Newtype Food Industrialization of Hubei University of Arts and Science~~
文摘In recent years, people have maked a great deal of investigation on and gained remarkable insight into the mechanism of chronicity of HBV infection, including: ①HBV antigenspecific cytotoxic T cells (CTL)undergo "activation-induced cell death (AICD)"more severely than usual,so they can’t eradicate HBV infected target cells; ②these CTL can also damage other immune active cells and contribute to forming wide immunosupression in hosts；③the balance between Th1 and Th2 cells’ response may be disturbed； ④ gene mutation and/or expression deficiency of antiviral cytokines and their receptors have occurred；⑤antigen presenting cells(APC) process and present vira antigens deficiently; ⑥some circulating immune complexes (CIC) may contribute to chronicity of HBV infection； ⑦hepatocytes can’t execute fully their cooperative function in immune response and regulation； ⑧HBV-specific T cells have suffered clonal deletion during the ontogeny period;⑨ HBxAg can trans-activate the human multidrug resistance (MDR)-1 gene and associated genes;and ⑩mutation of viral genome and antigen have emerged under host’s immune pressure. In this review,we have discussed all these items and pointed out that there still have many other questions to be researched and clarified.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
