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

Abstract：

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.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Kong FY,Chen W,He SJ,Lin ZM,Li X,Zhang XH,Yang XQ,Zhu FH,Tong XK,Zhou Y,Tang W,Duan WH,Zuo JP

doi

10.1038/aps.2013.14

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

921-9

issue

7

eissn

1671-4083

issn

1745-7254

pii

aps201314

journal_volume

34

pub_type

杂志文章

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