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Inhibition of rejection in murine islet xenografts by CTLA41g and CD40LIg gene transfer

Chinese Medical Journal 2010年第21期 3106-3109页

作者： ZHANG Jian LI Hua JIANG Nan WANG Guo-ying FU Bin-sheng WANG Gen-shu YANG Yang CHEN Gui-hua J Liver Transplantation Center the Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510630 China

Background Costimulatory signals play a vital role in T cell activation. Blockade of costimulatory pathway by CTLA4Ig or CD40LIg have enhanced graft survival in experimental transplantation models yet mechanisms remain *** investigated the effects of CTLA4Ig and CD40LIg gene transfer on islet xenografts rejection in *** Human islets were infected with recombinant adenoviruses containing CTLA4Ig and CD40LIg genes and implanted beneath the kidney capsule of diabetic rats. Levels of blood sugar, morphological changes, and survival of grafts were recorded. Expressions of CTLA4Ig, CD40LIg and insulin were detected by immunohistochemical staining and cytokines levels were quantified by enzyme-linked immunosorbent assay （ELISA）.Results Blood glucose levels in transplant rats decreased to normal level on the 2nd day post transplantation. The mean blood glucose in the control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig ＋CD40LIg cotransfected group increased on days 8, 24, 21, 68, post transplantation respectively. The grafts in control group, CTLA4Ig transfected group, CD40LIg transfected group and CTLA4Ig ＋ CD40LIg cotransfected group survived for （8±1）, （29±4）, （27±3）, and （74±10） days, respectively. Survival in CTLA4Ig ＋ CD40LIg cotransfected group was significantly longer. Survivals of CTLA4Ig transfected group and CD40LIg transfected group were significantly longer than control group. In controJ animals, serum interleukin-2 and tumor necrosis factor a concentration significantly increased within seven days post transplantation. Haematoxylin eosin staining of grafts showed live islets in situ of transplant rats without inflammatory cell infiltration. Immunohistochemical staining confirmed the expression of insulin at islets in all experimental *** Transfer of CTLA4Ig and CD40Llg genes, especially the cotransfer of both, inhibits rejection of murine islet xenografts. Downregulated expressions of Th1 cells rel

关键词： transplantation islet of langerhans CTLA4Ig CD40LIg immune tolerance

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Inhibition of rejection in murine islet xenografts by CTLA4Ig and CD40LIg gene transfer

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中华医学杂志(英文版) 2010年第21期123卷 3106-3109页

作者： Jian Zhang Hua Li Nan Jiang Guo-Ying Wang Bin-Sheng Fu Gen-Shu Wang Yang Yang Gui-Hua Chen Liver Transplantation Center the Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510630 China.

Background Costimulatory signals play a vital role in T cell *** of costimulatory pathway by CTLA41gor CD40Llg have enhanced graft survival in experimental transplantation models yet mechanisms remain *** investigated the effects of CTLA4lg and CD40Llg gene transfer on islet xenografts rejection in *** Human islets were infected with recombinant adenoviruses containing CTLA4lg and CD40Llg genes andimplanted beneath the kidney capsule of diabetic *** of blood sugar,morphological changes,and survival ofgrafts were *** of CTLA4lg,CD40Llg and insulin were detected by immunohistochemical staining andcytokines levels were quantified by enzyme-linked immunosorbent assay (ELISA).Results Blood glucose levels in transplant rats decreased to normal level on the 2nd day post *** blood glucose in the control group,CTLA4lg transfected group,CD40Llg transfected group and CTLA4lg +CD40Llg cotransfected group increased on days 8,24,21,68,post transplantation *** grafts in controlgroup,CTLA4lg transfected group,CD40Llg transfected group and CTLA4lg + CD40Llg cotransfected group survived for(8±1),(29±4),(27±3),and (74±10) days,*** in CTLA4lg + CD40Llg cotransfected group wassignificantly *** of CTLA4lg transfected group and CD40Llg transfected group were significantly longerthan control *** control animals,serum interleukin-2 and tumor necrosis factor a concentration significantlyincreased within seven days post *** eosin staining of grafts showed live islets in situ oftransplant rats without inflammatory cell *** staining confirmed the expression of insulin atislets in all experimental *** Transfer of CTLA4lg and CD40Llg genes,especially the cotransfer of both,inhibits rejection of murineislet *** expressions of Th1 cells related cytokines might be related to the ben

关键词： transplantation islet of langerhans CTLA4Ig CD40LIg immune tolerance

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γ-aminobutyric acid secreted from isletβ-cells modulates exocrine secretion in rat pancreas

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World Journal of Gastroenterology 2006年第19期12卷 3026-3030页

作者： Yong-Deuk Park Zheng-Yun Cui Guang Wu Hyung-Seo Park Hyoung-Jin Park Department of MedicoLife Science Youngdong University Chungbuk Korea Department of Physiology College of Medicine and Ilsong Institute of Life Science Hallym University Chuncheon Gangwon-do Korea Department of Physiology College of Medicine Konyang University Daejeon Korea

AIM： To investigate the role of endogenous γ-aminobutyric acid （GABA） in pancreatic exocrine secretion. METHODS： The isolated, vascularly perfused rat pancreas was employed in this study to eliminate the possible influences of extrinsic nerves and hormones. Cholecystokinin （CCK; 10 pmol/L） was intra-arterially given to stimulate exocrine secretion of the pancreas. RESULTS： Glutamine, a major precursor of GABA, which was given intra-arterially at concentrations of 1, 4 and 10 mmol/L, dose-dependently elevated the CCK-stimulated secretions of fluid and amylase in the normal pancreas. Bicuculline （10 μmol/L）, a GABAA receptor antagonist, blocked the enhancing effect of glutamine （4 mmol/L） on the CCK-stimulated exocrine secretions. Glutamine, at concentrations of 1, 4 and 10 mmol/L, dose-dependently increased the GABA concentration in portal effluent of the normal pancreas. The effects of glutamine on the CCK-stimulated exocrine secretion as well as the GABA secretion were markedly reduced in the streptozotocintreated pancreas. CONCLUSION： GABA could be secreted from β-cells into the isletoacinar portal system after administration of glutainine, and could enhance the CCK-stimulated exocrine secretion through GABAA receptors. Thus, GABA in islet β-cells is a hormone modulating pancreatic exocrine secretion.

关键词： GABA GABA receptor GABA secretion Cholecystokinin islet of langerhans Pancreas

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