Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production | |
Kong, Fang-yuan1; Chen, Wei1; He, Shi-jun1; Lin, Ze-min1; Li, Xin1; Zhang, Xiao-hui1; Yang, Xiao-qian1; Zhu, Feng-hua1; 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. |
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