Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression

被引：5
|
作者：
Xu, Hua [1 ,2 ,3 ]
Yu, Ai-Ling [3 ]
Zhao, Da-Peng [3 ]
Meng, Guang-Yuan [4 ]
Wang, Ling [5 ]
Shan, Min [3 ]
Hu, Nai-Xia [3 ]
Liu, Yun-Lin [3 ]
机构：
[1] Shandong First Med Univ, Affiliated Hosp 1, Dept Neurol, 16766 Jinshi Rd, Jinan 250014, Shandong, Peoples R China
[2] Shandong Prov Qianfoshan Hosp, Jinan 250014, Shandong, Peoples R China
[3] Taian City Cent Hosp, Dept Neurol, 29 Longtan Rd, Tai An 271000, Shandong, Peoples R China
[4] Taian City Cent Hosp, Clin Lab, Tai An 271000, Shandong, Peoples R China
[5] Taian City Cent Hosp, Dept Hematol, Tai An 271000, Shandong, Peoples R China
来源：
INNATE IMMUNITY | 2022年 / 28卷 / 05期
基金：
中国国家自然科学基金;
关键词：
Ursolic acid; Th17 cell differentiation; Th17 cell migration; Schwann cells; ROR-GAMMA-T; STAT3; PHENOTYPE; ARTHRITIS; TARGETS; BETA;
D O I：
10.1177/17534259221094559
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Th17 cells represent important immune cells. Ursolic acid (UA) can regulate immune cell activities. This study was aimed to explore the effects of UA on Th17 cell differentiation and Schwann cell(SCs)-mediated migration and the potential mechanism. Naive CD4(+) T cells were isolated from rat peripheral blood, induced for Th17 cell differentiation, and treated with UA. The proportion of Th17 cells was detected by flow cytometry assay. SCs were co-cultured with Th17 cells. Th17 cell migration was detected by Transwell assay. The molecule expression was determined by Western blot and qRT-PCR. UA inhibited the Th17 cell differentiation and suppressed the STAT3/ROR gamma t pathway. STAT3 overexpression up-regulated p-STAT3 and ROR gamma t expression and promoted Th17 cell differentiation under the UA treatment. In LPS- and IFN-gamma-stimulated-SCs, UA suppressed the expression of chemokines CXCL9/10, but had no significant effect of CCL20 expression. The expression CXCL9/10 receptor CXCR3 was higher in Th17 cells than that in Treg cells, while the expression CCL20 receptor CCR6 was lower in Th17 cells than that in Treg cells. UA, anti-CXCR3, and anti-CCR6 treatment inhibited SCs-mediated Th17 cell migration, and anti-CXCR3 exerted stronger inhibitory effect than Anti-CCR6. UA inhibited Th17 cell differentiation through STAT3/ROR gamma t pathway and suppressed Th17 cell migration through down-regulating CXCL9/10 expression in SCs.
引用
收藏
页码：155 / 163
页数：9
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