Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China.
Inflammation. 2019 Oct;42(5):1530-1541. doi: 10.1007/s10753-019-01015-z.
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-γt, 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-γt, and STAT3 in colonic tissue. ATX-LPA axis blockade could alleviate inflammation by suppressing Th17 cell differentiation in chronic UC.
自分泌酶-溶血磷脂酸（ATX-LPA）轴与几种炎症相关疾病密切相关。在慢性溃疡性结肠炎（UC）患者的结肠黏膜中，发现 ATX 的表达和 Th17 细胞的百分比增加。然而，ATX-LPA 轴是否影响慢性 UC 中 Th17 细胞的分化尚不清楚。为了研究 ATX-LPA 轴是否有助于 Th17 细胞分化，通过间歇性饮用 DSS 水建立了慢性 UC 的小鼠模型，并使用 ATX 抑制剂进行干预。观察疾病活动指数（DAI）、结肠重量与长度比、结肠长度、结肠组织病理学、MAdCAM-1 以及结肠组织中 ATX、LPA 受体、CD34、IL-17A、IL-21、IL-6、ROR-γt、STAT3 的表达和脾脏及肠系膜淋巴结（MLN）中 Th17 细胞的百分比。使用不同方法测量。ATX 阻断能够缓解 DSS 诱导的慢性结肠炎的症状和炎症反应。DAI 和结肠重量与长度比明显降低，而结肠长度增加。抑制剂组的病理损伤和结肠炎严重程度比 DSS 组轻。抑制 ATX 降低了 ATX、LPA 受体和 CD34 的表达，也降低了脾脏和 MLN 中 Th17 细胞的百分比，以及 Th17 细胞信号通路中的因子，包括 IL-17A 和 IL-21，以及结肠组织中的 IL-6、ROR-γt 和 STAT3。ATX-LPA 轴阻断通过抑制慢性 UC 中 Th17 细胞分化来缓解炎症。
