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Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin

Introduction The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mou...

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Published in:Advances in therapy 2008-12, Vol.25 (12), p.1331-1341
Main Authors: Wang, Jiang, Zhao, Rong, Zhang, Fuqin, Li, Jianping, Huo, Binliang, Cao, Yunxin, Dou, Kefeng
Format: Article
Language:English
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Summary:Introduction The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes. Methods BALB/c (H-2K d ) recipient mice ( n =70) were divided into seven groups ( n =10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2K b ) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4–6 received SMS 201–995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4 + CD25 + Foxp3 high regulatory T cells (T reg ) were generated in vivo. Results BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively; P
ISSN:0741-238X
1865-8652
DOI:10.1007/s12325-008-0121-z