Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production
Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production
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霉酚酸衍生物 118 通过抑制 IL-17 的产生来改善皮肤移植的效果
DOI：
10.1038/aps.2013.14
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发表时间：
2013-05
影响因子：
8.2
通讯作者：
Zuo, Jian-ping
中科院分区：
文献类型：
--
作者：
Zhou, Yu;Tang, Wei;Duan, Wen-hu;Zuo, Jian-ping
目的：探讨新型霉酚酸衍生物118对小鼠同种异体皮肤移植模型的作用及其机制。方法：将BALB/c小鼠的尾部皮肤移植到C57 BL/6小鼠的皮床上（同种异体），或将雌性C57 BL/6小鼠的尾部皮肤移植到雌性C57 BL/6小鼠的皮床上（同体）。移植前3d和移植后10 d分别给予衍生物118（40 mg· kg-1· d-1，po）治疗13 d。分离皮肤移植物、脾细胞和移植物浸润的淋巴细胞并离体检查。结果：衍生物118能显著提高小鼠同种异体皮肤移植物的存活率。流式细胞仪分析和H&E染色显示，该衍生物显着减少炎性细胞浸润到移植物中。趋化因子CXCL 1、CXCL 2、CCL 7和CCL 2的水平在衍生物118处理的移植物中降低。此外，衍生物118显著抑制移植物中的IL-17水平，但不影响鼠同种异体皮肤移植物模型中系统性辅助T细胞的分化。此外，IL-23 p19表达在衍生物118处理组的移植物中受到抑制，这可能是由于TLR 4和MyD 88表达的降低。最后，衍生物118没有发挥直接影响辅助性T细胞分化在vitro.Conclusion：治疗与霉酚酸衍生物118提高小鼠同种异体皮肤移植物通过降低IL-23的表达和抑制局部IL-17的分泌在移植物中，而不是直接抑制Th 17分化。
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.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1172/jci17573
发表时间：
2003-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
D. Goldstein;B. Tesar;S. Akira;Fadi G Lakkis
通讯作者：
D. Goldstein;B. Tesar;S. Akira;Fadi G Lakkis
影响因子：
3.7
作者：
Hou LF;He SJ;Li X;Wan CP;Yang Y;Zhang XH;He PL;Zhou Y;Zhu FH;Yang YF;Li Y;Tang W;Zuo JP
通讯作者：
Zuo JP
影响因子：
2.1
作者：
Sihua Wang;Jun Li;A. Xie;Guo-hua Wang;Ni Xia;P. Ye;L. Rui;J. Xia
通讯作者：
Sihua Wang;Jun Li;A. Xie;Guo-hua Wang;Ni Xia;P. Ye;L. Rui;J. Xia
影响因子：
4.4
作者：
Mathur, Anubhav N.;Chang, Hua-Chen;Kaplan, Mark H.
通讯作者：
Kaplan, Mark H.