The immunoregulation effect of alpha 1-antitrypsin prolong β-cell survival after transplantation.
Islet transplantation has considerable potential as a cure for diabetes. However, the difficulties that arise from inflammation and the immunological rejection of transplants must be addressed for islet transplantation to be successful. Alpha 1-antitrypsin (AAT) inhibits the damage on β cells caused by inflammatory reactions and promotes β-cell survival and proliferation. This protein also induces specific immune tolerance to transplanted β cells. However, whether the expression of AAT in β cells themselves could eliminate or decrease immunological rejection of transplants is not clear. Therefore, we established a β cell line (NIT-hAAT) that stably expresses human AAT. Interestingly, in a cytotoxic T lymphocyte (CTL)-killing assay, we found that hAAT reduced apoptosis and inflammatory cytokine production in NIT-1 cells and regulated the Th1/Th2 cytokine balance in vitro. In vivo transplantation of NIT-hAAT cells into mice with diabetes showed hAAT inhibited immunological rejection for a short period of time and increased the survival of transplanted β cells. This study demonstrated that hAAT generated remarkable immunoprotective and immunoregulation effects in a model of β cell islet transplantation for diabetes model.
Department of Cardiac Surgery, General Hospital of Ningxia Medical University, Yinchuan, PR China; The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China.
Yun
Y
Wang
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China.
Hong-Jie
HJ
Yan
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China.
Shu-Yan
SY
Zhou
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China.
Yun-Shuang
YS
Wang
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China.
Hui
H
Qi
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China.
Chun-Yan
CY
Deng
The Key Laboratory of Stem Cell and Cellular Therapy, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, PR China; Shenzhen Institution of Gerontology, Shenzhen, PR China.
Fu-Rong
FR
Li
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000235:genetics*; D056747:Immunomodulation / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D058408:Th1-Th2 Balance; D019076:Transgenes; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000276:immunology
D007155:Immunologic Factors; D000515:alpha 1-Antitrypsin