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15-Deoxy-△12,14-Prostaglandin J2 Promotes Resolution of Experimentally Induced Colitis : 15-Deoxy-Delta(12,14)-Prostaglandin J(2) Promotes Resolution of Experimentally Induced Colitis

Cited 6 time in Web of Science Cited 6 time in Scopus
Authors

Kim, Wonki; Jang, Jeong-Hoon; Zhong, Xiancai; Seo, HyungseokSurh, Young-Joon

Issue Date
2021-02
Publisher
Frontiers Media S.A.
Citation
Frontiers in Immunology, Vol.12
Abstract
Uncontrolled macrophage functions cause failure to resolve gut inflammation and has been implicated in the pathogenesis of inflammatory bowel disease (IBD). 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), one of endogenous lipid mediators formed from arachidonic acid during the inflammatory process, has been reported to terminate inflammation. However, the pro-resolving effect of 15d-PGJ(2) on intestinal inflammation and underlying molecular mechanisms remain largely unknown. In the present study, we examined the effects of 15d-PGJ(2) on the resolution of dextran sulfate sodium (DSS)-induced murine colitis that mimics human IBD. Pharmacologic inhibition of prostaglandin D synthase (PGDS) responsible for the synthesis of 15d-PGJ(2) hampered resolution of inflammation in the colonic mucosa of mice treated with DSS. Notably, intraperitoneal injection of 15d-PGJ(2) accelerated the resolution of experimentally induced colitis. 15d-PGJ(2) treatment reduced the number of neutrophils and M1 macrophages, while it increased the proportion of M2 macrophages. Moreover, 15d-PGJ(2) treated mice exhibited the significantly reduced proportion of macrophages expressing the pro-inflammatory cytokine, IL-6 with concomitant suppression of STAT3 phosphorylation in the colonic mucosa of mice administered 2.5% DSS in drinking water. Taken together, these findings clearly indicate that 15d-PGJ(2), endogenously generated from arachidonic acid by cyclooxygenase-2 and PGDS activities in inflamed tissue, promotes resolution of intestinal colitis.
ISSN
1664-3224
URI
https://hdl.handle.net/10371/178057
DOI
https://doi.org/10.3389/fimmu.2021.615803
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