AIM To assess the possible roles of cytokines (TNF α, IFN γ, IL 6 and IL 8) in liver damage of hepatitis B. METHODS The serum TNF α, IFN γ, IL 6 and IL 8 were detected by ELISA in 66 patients with hepat...AIM To assess the possible roles of cytokines (TNF α, IFN γ, IL 6 and IL 8) in liver damage of hepatitis B. METHODS The serum TNF α, IFN γ, IL 6 and IL 8 were detected by ELISA in 66 patients with hepatitis B and 20 healthy blood donors. RESULTS TNF α and IL 6 in all types of clinical hepatitis B were significantly higher than those in healthy blood donors ( P <0 05); meanwhile the levels of TNF α, IFN γ, IL 6 and IL 8 in the patients with fulminant hepatitis B were much higher than those in the patients with acute hepatitis B ( P <0 05); the level of TNF α was positively correlated with the levels of IFN γ, Il 6 and IL 8 in all types of hepatitis B ( r IFN =0 24, r IL 6 =0 35, r IL 8 =0 44) and the TNF α, IFN γ, IL 6 and IL 8 were positively correlated with serum bilirubin ( P <0 05). Dynamic changes of these cytokines were observed in the course of acute and fulminant hepatitis. The level of IFN γ peaked in the initial period of acute hepatitis and early stage of hepatic coma in fulminant hepatitis; TNF α, IL 6 and IL 8 increased with exacerbation, and reached a peak when the liver damage was most serious, then decreased when patient conditions were improved. CONCLUSION The increased cytokines were related to the inflammation of liver cells and multiple factors may play certain roles in liver damage.展开更多
Bone-marrow-derived mesenchymal stem cells （MSCs） have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability o...Bone-marrow-derived mesenchymal stem cells （MSCs） have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability of MSCs. The precise mechanisms underlying MSC-mediated immunosuppression remain largely undefined, although both cell-cell contact and soluble factors have been implicated; nor is it clear how the immunosuppressive property of MSCs is modulated by T cells. Using MSCs isolated from mouse bone marrow, we show here that interferon gamma （IFNγ）, a well-known proinflammatory cytokine produced by activated T cells, plays an important role in priming the immunosuppressive property of MSCs. Mechanistically, IFNγ acts directly on MSCs and leads to up-regulation of B7-H1, an inhibitory surface molecule in these stem cells. MSCs primed by activated T cells derived from IFNγ-/- mouse exhibited dramatically reduced ability to suppress T cell proliferation, a defect that can be rescued by supplying exogenous IFNγ. Moreover, siRNA-mediated knockdown of B7-H1 in MSCs abolished immunosuppression by these cells. Taken together, our results suggest that IFNγ plays a critical role in triggering the immunosuppresion by MSCs through upregulating B7-H1 in these cells, and provide evidence supporting the cell-cell contact mechanism in MSC-mediated immunosuppression.展开更多
文摘AIM To assess the possible roles of cytokines (TNF α, IFN γ, IL 6 and IL 8) in liver damage of hepatitis B. METHODS The serum TNF α, IFN γ, IL 6 and IL 8 were detected by ELISA in 66 patients with hepatitis B and 20 healthy blood donors. RESULTS TNF α and IL 6 in all types of clinical hepatitis B were significantly higher than those in healthy blood donors ( P <0 05); meanwhile the levels of TNF α, IFN γ, IL 6 and IL 8 in the patients with fulminant hepatitis B were much higher than those in the patients with acute hepatitis B ( P <0 05); the level of TNF α was positively correlated with the levels of IFN γ, Il 6 and IL 8 in all types of hepatitis B ( r IFN =0 24, r IL 6 =0 35, r IL 8 =0 44) and the TNF α, IFN γ, IL 6 and IL 8 were positively correlated with serum bilirubin ( P <0 05). Dynamic changes of these cytokines were observed in the course of acute and fulminant hepatitis. The level of IFN γ peaked in the initial period of acute hepatitis and early stage of hepatic coma in fulminant hepatitis; TNF α, IL 6 and IL 8 increased with exacerbation, and reached a peak when the liver damage was most serious, then decreased when patient conditions were improved. CONCLUSION The increased cytokines were related to the inflammation of liver cells and multiple factors may play certain roles in liver damage.
基金Acknowledgments We thank Dr Yi Zhang （Department of Cell Biology, Institute of Basic Medical Sciences, Beijing, China） for helpful discussions. This work was supported by National Basic Research Program of China （Grant No. 2005CB5227053）, National Natural Science Foundation of China （Grant No. 30671945）, Science and Technology Commission of Shanghai Municipality （No. 06JC 14044 and 07JC 14070）, Shanghai Leading Academic Discipline Project （T0206）, Shanghai Institute of Immunology Academic Project （No. 07-A04, to Ningli Li） and Leading Academic discipline project （IRT0637, Education ministry of China）.
文摘Bone-marrow-derived mesenchymal stem cells （MSCs） have been shown to possess immunosuppressive properties, e.g., by inhibiting T cell proliferation. Activated T cells can also enhance the immunosuppression ability of MSCs. The precise mechanisms underlying MSC-mediated immunosuppression remain largely undefined, although both cell-cell contact and soluble factors have been implicated; nor is it clear how the immunosuppressive property of MSCs is modulated by T cells. Using MSCs isolated from mouse bone marrow, we show here that interferon gamma （IFNγ）, a well-known proinflammatory cytokine produced by activated T cells, plays an important role in priming the immunosuppressive property of MSCs. Mechanistically, IFNγ acts directly on MSCs and leads to up-regulation of B7-H1, an inhibitory surface molecule in these stem cells. MSCs primed by activated T cells derived from IFNγ-/- mouse exhibited dramatically reduced ability to suppress T cell proliferation, a defect that can be rescued by supplying exogenous IFNγ. Moreover, siRNA-mediated knockdown of B7-H1 in MSCs abolished immunosuppression by these cells. Taken together, our results suggest that IFNγ plays a critical role in triggering the immunosuppresion by MSCs through upregulating B7-H1 in these cells, and provide evidence supporting the cell-cell contact mechanism in MSC-mediated immunosuppression.
