Autotaxin-Lysophosphatidic Acid Axis Blockade Improves Inflammation by Regulating Th17 Cell Differentiation in DSS-Induced Chronic Colitis Mice

被引：28

作者：

Dong, Ya-Lan ^{[1
]}

Duan, Xue-Yun ^{[2
,3
]}

Liu, Yu-Jin ^{[1
]}

Fan, Heng ^{[1
]}

Xu, Meng ^{[1
]}

Chen, Qian-Yun ^{[1
]}

Nan, Zhen ^{[1
]}

Wu, Hui ^{[1
]}

Deng, Shuang-Jiao ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Integrated Tradit Chinese & Western Med, Wuhan 430022, Hubei, Peoples R China

[2] Hubei Prov Hosp Tradit Chinese Med, Wuhan 430061, Hubei, Peoples R China

[3] Hubei Prov Acad Tradit Chinese Med, Wuhan 430074, Hubei, Peoples R China

来源：

INFLAMMATION | 2019年 / 42卷 / 05期

基金：

中国国家自然科学基金;

关键词：

ulcerative colitis (UC); autotaxin (ATX); lysophosphatidic acid (LPA); Th17 cell differentiation; OVARIAN-CANCER CELL; ULCERATIVE-COLITIS; LYSOPHOSPHOLIPASE-D; PULMONARY-FIBROSIS; COLORECTAL-CANCER; T(H)17 CELLS; EXPRESSION; LPA; PATHOGENESIS; INHIBITION;

D O I：

10.1007/s10753-019-01015-z

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Autotaxin-lysophosphatidic acid (ATX-LPA) axis is closely associated with several inflammation-related diseases. In the colonic mucosa of patients with chronic ulcerative colitis (UC), the expression of ATX and the percentage of Th17 cells are found to increase. However, it is unclear whether ATX-LPA axis affects the differentiation of Th17 cells in chronic UC. To investigate whether ATX-LPA axis contributes to Th17 cell differentiation, a mouse model of chronic UC was established by drinking water with DSS at intervals. ATX inhibitor was used as an intervention. The disease active index (DAI), colonic weight to length ratio, colon length, colon histopathology, and MAdCAM-1 were observed. Additionally, the expression of ATX, LPA receptor, CD34, IL-17A, IL-21, IL-6, ROR-gamma t, STAT3 in colonic tissue, and the percentage of Th17 cells in spleens and mesenteric lymph nodes (MLNs) were measured using different methods. ATX blockade was able to relieve symptoms and inflammatory response of DSS-induced chronic colitis. The DAI and colonic weight to length ratio were apparently decreased, while the colon length was increased. The pathological damage and colitis severity were lighter in the inhibitor group than that in the DSS group. Inhibiting ATX reduced the expression of ATX, LPA receptor, and CD34 and also decreased the percentages of Th17 cells in spleens and MLNs and the expressions of IL-17A and IL-21, as well as the factors in Th17 cell signaling pathway including IL-6, ROR-gamma t, and STAT3 in colonic tissue. ATX-LPA axis blockade could alleviate inflammation by suppressing Th17 cell differentiation in chronic UC.

引用

页码：1530 / 1541

页数：12

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