AIM: To investigate the protective effect against two immune liver injury models in mice by 2-amino-2-[2-(4-octylphenyl) ethyl] propane-l,3-diol hydrochloride and its possible mechanisms in Con A-induced liver damage....AIM: To investigate the protective effect against two immune liver injury models in mice by 2-amino-2-[2-(4-octylphenyl) ethyl] propane-l,3-diol hydrochloride and its possible mechanisms in Con A-induced liver damage. METHODS: Liver tissue or hepatocyte injury was monitored biochemically by measuring alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) activity. Hematoxylin & eosin (HE) staining was used for histopathological examination. To evaluate the role of IFN-γ and IL-4 in the liver injury, serum levels of IFN-γ and IL-4 were determined using commercially available ELISA kit at 12 h after Con A challenge. We also determined FTY 720-induced spleen cell apoptosis by flow cytometry analysis or spleen cell proliferation test. RESULTS: Different doses of FTY 720 treatment dramatically reduced circulating markers of hepatocyte injury in two kinds of immunological liver injury models. FTY 720 dramatically reduced the elevated serum IFN-γ and IL-4 levels after Con A injection. Effect of spleen cell supernatants treated with Con A or FTY 720 on hepatocytes showed that ALT activities in cultured hepatocyte supernatants in Con A treatment group increased markedly and FTY 720 could reduce this elevated ALT activities in FTY 720 treatment group. FTY 720 dose-dependently increased the percentage of apoptotic cells in T cells and inhibited splenocyte proliferation induced by Con A. CONCLUSION: Pretreatment with FTY 720 was shown to produce protective effect on the immune liver injury in mice. The possible mechanism of FTY 720 on Con A-induced liver damage is that it could inhibit lymphocyte proliferation and induce lymphocyte apoptosis, resulting in the reduction of IL-4 or IFN-γ release, and subsequently protecting liver from being damaged by Con A.展开更多
Our previous study has demonsstrated that donor specific graft tolerance can be induced by donor spleen cells from dexamethasone (DEX ) triated rats (DEX SPC). In this study we investigated if FTY 720. a new immunosup...Our previous study has demonsstrated that donor specific graft tolerance can be induced by donor spleen cells from dexamethasone (DEX ) triated rats (DEX SPC). In this study we investigated if FTY 720. a new immunosuppressant. could have a synergistic effect with DEX -SPC on the tolerance inductivity. The results showed that graft survival was further prolonged in reedients receiving both preoperative higher dose (10 mg/kg daily ) FTY 720 and DEX-SPC. However. the preoperative low dose (1 mg /kg daily ) FTY 720 did not show any syner gistic effect on tolerance induction with DEX -SPC. Unexpectedly in the perioperative regimen the lower dose FTY 720 had a synergistic effect with DEX -SPC. while the higher dose did not have. in prolonging graft survival. It is indicated that FTY 720 synergistically helps DEX-SPC to induce tolerance .The results also reinforce the viewpoint that the fortune of an allograft. tolerallced or rejected id not determjned by the nature of donor antigen, but is the function of antigen presentation and recipient T cells . Furthermore . the authors also proposed ’the way and frequency of antigen presentation model ’to interpret the apparently paradoxical results .展开更多
Objective: To investigate the significance of FTY 720 in combination with donor spleen cells in allogeneic tolerance induction. Methods: Different doses of FTY720 (1 mg· kg 1d1 or 10 mg· kg －1d －1 ) and di...Objective: To investigate the significance of FTY 720 in combination with donor spleen cells in allogeneic tolerance induction. Methods: Different doses of FTY720 (1 mg· kg 1d1 or 10 mg· kg －1d －1 ) and different number of donor spleen cells (5 ×107ｏr 5×108 ) were preoperatively administrated into rat cardiac allograft recipients. Resuits: It showed that FTY 720 had a synergistic effect with donor spleen cells on prolonging allograft survival as compared with FTY 720 alone. The number of donor spleen cells and FTY 720 doses are important factors influencing allograft curvival . Conclusion: It is suggested that allogeneic tolerance induction is related to the ways and frequency of antigen presentation by donor APC to recipient T cells.展开更多
Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)i...Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.展开更多
文摘AIM: To investigate the protective effect against two immune liver injury models in mice by 2-amino-2-[2-(4-octylphenyl) ethyl] propane-l,3-diol hydrochloride and its possible mechanisms in Con A-induced liver damage. METHODS: Liver tissue or hepatocyte injury was monitored biochemically by measuring alanine aminotransferase (sALT) and aspartate aminotransferase (sAST) activity. Hematoxylin & eosin (HE) staining was used for histopathological examination. To evaluate the role of IFN-γ and IL-4 in the liver injury, serum levels of IFN-γ and IL-4 were determined using commercially available ELISA kit at 12 h after Con A challenge. We also determined FTY 720-induced spleen cell apoptosis by flow cytometry analysis or spleen cell proliferation test. RESULTS: Different doses of FTY 720 treatment dramatically reduced circulating markers of hepatocyte injury in two kinds of immunological liver injury models. FTY 720 dramatically reduced the elevated serum IFN-γ and IL-4 levels after Con A injection. Effect of spleen cell supernatants treated with Con A or FTY 720 on hepatocytes showed that ALT activities in cultured hepatocyte supernatants in Con A treatment group increased markedly and FTY 720 could reduce this elevated ALT activities in FTY 720 treatment group. FTY 720 dose-dependently increased the percentage of apoptotic cells in T cells and inhibited splenocyte proliferation induced by Con A. CONCLUSION: Pretreatment with FTY 720 was shown to produce protective effect on the immune liver injury in mice. The possible mechanism of FTY 720 on Con A-induced liver damage is that it could inhibit lymphocyte proliferation and induce lymphocyte apoptosis, resulting in the reduction of IL-4 or IFN-γ release, and subsequently protecting liver from being damaged by Con A.
文摘Our previous study has demonsstrated that donor specific graft tolerance can be induced by donor spleen cells from dexamethasone (DEX ) triated rats (DEX SPC). In this study we investigated if FTY 720. a new immunosuppressant. could have a synergistic effect with DEX -SPC on the tolerance inductivity. The results showed that graft survival was further prolonged in reedients receiving both preoperative higher dose (10 mg/kg daily ) FTY 720 and DEX-SPC. However. the preoperative low dose (1 mg /kg daily ) FTY 720 did not show any syner gistic effect on tolerance induction with DEX -SPC. Unexpectedly in the perioperative regimen the lower dose FTY 720 had a synergistic effect with DEX -SPC. while the higher dose did not have. in prolonging graft survival. It is indicated that FTY 720 synergistically helps DEX-SPC to induce tolerance .The results also reinforce the viewpoint that the fortune of an allograft. tolerallced or rejected id not determjned by the nature of donor antigen, but is the function of antigen presentation and recipient T cells . Furthermore . the authors also proposed ’the way and frequency of antigen presentation model ’to interpret the apparently paradoxical results .
文摘Objective: To investigate the significance of FTY 720 in combination with donor spleen cells in allogeneic tolerance induction. Methods: Different doses of FTY720 (1 mg· kg 1d1 or 10 mg· kg －1d －1 ) and different number of donor spleen cells (5 ×107ｏr 5×108 ) were preoperatively administrated into rat cardiac allograft recipients. Resuits: It showed that FTY 720 had a synergistic effect with donor spleen cells on prolonging allograft survival as compared with FTY 720 alone. The number of donor spleen cells and FTY 720 doses are important factors influencing allograft curvival . Conclusion: It is suggested that allogeneic tolerance induction is related to the ways and frequency of antigen presentation by donor APC to recipient T cells.
基金supported by grants from the National Natural Science Foundation of China,No.81971231(to JL)Liaoning Revitalization Talents Program,No.XLYC1907178(to JL)。
文摘Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.
