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RIPK1 inhibitor ameliorates colitis by directly maintaining intestinal barrier homeostasis and regulating following IECs-immuno crosstalk

文献类型：期刊论文

作者Lu, Huimin1,2; Li, Heng1,2; Fan, Chen2; Qi, Qing2; Yan, Yuxi1,2; Wu, Yanwei2; Feng, Chunlan2; Wu, Bing1,2; Gao, Yuanzhuo1,2; Zuo, Jianping1,2
刊名BIOCHEMICAL PHARMACOLOGY
出版日期2020-02-01
卷号172页码:16
关键词RIPK1 inhibitor Colitis Barrier homeostasis IECs-immunocytes crosstalk Necroptosis NF-kappa B
ISSN号0006-2952
DOI10.1016/j.bcp.2019.113751
通讯作者Zuo, Jianping(jpzuo@simm.ac.cn) ; Tang, Wei(tangwei@simm.ac.cn)
英文摘要Background: The receptor-interacting protein kinase 1 (RIPK1) has emerged as a key upstream regulator that controls the inflammatory response via its kinase-dependent and independent functions, which makes it an attractive target for developing new drugs against inflammation-related diseases. Growing evidences illustrate that RIPK1 is certainly associated with pathogenesis of multiple tissue-damage diseases. However, what are intricate regulatory codes of RIPK1 inhibitor in diseases is still obscure. Methods: We used DSS-induced colitis model in vivo to study the therapeutic effects and the mechanisms of RIPK1 inhibitor. We next characterized the barrier function and the interaction between intestinal epithelial cells (IECs) and immunocytes both in vivo and in vitro. As a candidate in clinical study, GSK2982772 is the most well-developed drug of RIPK1 inhibitors, and we chose it as our study object. Results: We demonstrated that RIPK1 inhibitor could ameliorate the intestinal barrier injury by reducing tight junctions' disruption and accompanying oxidative stress. Moreover, the release of chemokines and adhesion molecules from damaged IECs was suppressed by RIPK1 inhibitor treatment. And these protective effects were not only dependent on the suppression of necroptosis but also on the compromised activity of NF-kappa B. Taken together, RIPK1 inhibitor exerts suppressive function in intestinal inflammatory response possibly via protecting the intestinal epithelial barrier and maintaining the homeostasis of immune microenvironments. Eventually, the positive feedback immune response which triggered progressive epithelial cells injury could be restrained.
WOS关键词ULCERATIVE-COLITIS ; INFLAMMATION ; NECROPTOSIS ; APOPTOSIS ; RECEPTOR ; MIGRATION ; CELLS ; TRAFFICKING ; NECROSIS ; DISEASE
资助项目Personalized Medicines-Molecular Signature-based Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020370] ; Science & Technology Commission of Shanghai Municipality, China[18431907100]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000527332100014
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/280483]  
专题新药研究国家重点实验室
通讯作者Zuo, Jianping; Tang, Wei
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Lu, Huimin,Li, Heng,Fan, Chen,et al. RIPK1 inhibitor ameliorates colitis by directly maintaining intestinal barrier homeostasis and regulating following IECs-immuno crosstalk[J]. BIOCHEMICAL PHARMACOLOGY,2020,172:16.
APA Lu, Huimin.,Li, Heng.,Fan, Chen.,Qi, Qing.,Yan, Yuxi.,...&Tang, Wei.(2020).RIPK1 inhibitor ameliorates colitis by directly maintaining intestinal barrier homeostasis and regulating following IECs-immuno crosstalk.BIOCHEMICAL PHARMACOLOGY,172,16.
MLA Lu, Huimin,et al."RIPK1 inhibitor ameliorates colitis by directly maintaining intestinal barrier homeostasis and regulating following IECs-immuno crosstalk".BIOCHEMICAL PHARMACOLOGY 172(2020):16.

入库方式： OAI收割

来源：上海药物研究所

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