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

doi:10.1016/j.bcp.2019.113751

	RIPK1 inhibitor ameliorates colitis by directly maintaining intestinal barrier homeostasis and regulating following IECs-immuno crosstalk
	Lu, Huimin 1,2; Li, Heng 1,2; Fan, Chen 2; Qi, Qing 2; Yan, Yuxi 1,2; Wu, Yanwei 2; Feng, Chunlan 2; Wu, Bing 1,2; Gao, Yuanzhuo 1,2; Zuo, Jianping 1,2
刊名	BIOCHEMICAL PHARMACOLOGY
	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
DOI	10.1016/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.
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关键词	ULCERATIVE-COLITIS ; INFLAMMATION ; NECROPTOSIS ; APOPTOSIS ; RECEPTOR ; MIGRATION ; CELLS ; TRAFFICKING ; NECROSIS ; DISEASE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000527332100014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280483]
专题	中国科学院上海药物研究所
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.