Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production

doi:10.1038/aps.2013.14

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	Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production
	Kong, Fang-yuan 1; Chen, Wei 1; He, Shi-jun1 ; Lin, Ze-min 1; Li, Xin 1; Zhang, Xiao-hui 1; Yang, Xiao-qian 1; Zhu, Feng-hua 1; Tong, Xian-kun1 ; Zhou, Yu1
刊名	ACTA PHARMACOLOGICA SINICA
	2013-07
卷号	34 期号:7 页码:921-929
关键词	mycophenolate mofetil derivative 118 transplantation skin graft allograft syngraft IL-17 IL-23
ISSN号	1671-4083
DOI	10.1038/aps.2013.14
文献子类	Article
英文摘要	Aim: To investigate the effects and underlying mechanisms of 118, a novel derivative of mycophenolic acid, in a murine allogeneic skin graft model. Methods: Skin grafts were conducted by grafting BALB/c donor tail skin into C57BL/6 skin beds (allograft) or by grafting female C57BL/6 donor tail skin into female C57BL/6 skin beds (syngraft). The mice were treated with the derivative 118 (40 mg.kg(-1).d(-1), po) for 13 d (3 d before and 10 d after transplantation). Skin grafts, splenocytes and graft-infiltrated lymphocytes were isolated and examined ex vivo. The effects of the derivative 118 on naive CD4(+) T cell differentiation were examined in vitro. Results: Treatment with the derivative 118 dramatically increased the survival rate of murine allogeneic skin grafts. Flow cytometric analysis and H&E staining showed that the derivative significantly decreased inflammatory cell infiltration into the grafts. The levels of the chemokines CXCL1, CXCL2, CCL7, and CCL2 were reduced in the derivative 118-treated grafts. Additionally, the derivative 118 significantly suppressed the IL-17 levels in the grafts but did not affect the differentiation of systemic helper T cells in the murine allogeneic skin graft model. Furthermore, IL-23p19 expression was suppressed in the grafts from the derivative 118-treated group, which might be due to decreases in TLR4 and MyD88 expression. Finally, the derivative 118 did not exert direct influences on helper T cell differentiation in vitro. Conclusion: Treatment with the mycophenolic acid derivative 118 improves murine allogeneic skin grafts by decreasing IL-23 expression and suppressing local IL-17 secretion in the grafts, rather than directly inhibiting Th17 differentiation.
资助项目	National Natural Science Foundation of China (NSFC)[81072652] ; National Natural Science Foundation of China (NSFC)[81273524] ; National Natural Science Foundation of China (NSFC)[81273525]
WOS关键词	ALLOGRAFT-REJECTION ; MOFETIL ; CELLS ; INTERLEUKIN-17 ; TRANSPLANTATION ; TH17 ; INFLAMMATION ; COMMITMENT ; EXPRESSION ; CHEMOKINE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:4874886
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000321332700008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277555]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药物化学研究室
通讯作者	Tang, Wei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Kong, Fang-yuan,Chen, Wei,He, Shi-jun,et al. Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production[J]. ACTA PHARMACOLOGICA SINICA,2013,34(7):921-929.
APA	Kong, Fang-yuan.,Chen, Wei.,He, Shi-jun.,Lin, Ze-min.,Li, Xin.,...&Zuo, Jian-ping.(2013).Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production.ACTA PHARMACOLOGICA SINICA,34(7),921-929.
MLA	Kong, Fang-yuan,et al."Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production".ACTA PHARMACOLOGICA SINICA 34.7(2013):921-929.