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Prostanoids, especially prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>), are well-characterized mediators of inflammation. PGE<jats:sub>2<\/jats:sub>is produced in an inducible manner in macrophages (M\u03d5) by microsomal PGE<jats:sub>2<\/jats:sub>-synthase-1 (mPGES-1), with the notion that it also conveys pro-resolving properties. We aimed to characterize the role of mPGES-1 during resolution of acute, zymosan-induced peritonitis. Experimentally, we applied the mPGES-1 inhibitor compound III (CIII) once the inflammatory response was established and confirmed its potent PGE<jats:sub>2<\/jats:sub>-blocking efficacy. mPGES-1 inhibition resulted in an incomplete removal of neutrophils and a concomitant increase in monocytes and M\u03d5 during the resolution process. The mRNA-seq analysis identified enhanced C-X3-C motif receptor 1 (CX3CR1) expression in resident and infiltrating M\u03d5 upon mPGES-1 inhibition. Besides elevated<jats:italic>Cx3cr1<\/jats:italic>expression, its ligand CX3CL1 was enriched in the peritoneal lavage of the mice, produced by epithelial cells upon mPGES-1 inhibition. CX3CL1 not only increased adhesion and survival of M\u03d5 but its neutralization also completely reversed elevated inflammatory cell numbers, thereby normalizing the cellular, peritoneal composition during resolution. Our data suggest that mPGES-1-derived PGE<jats:sub>2<\/jats:sub>contributes to the resolution of inflammation by preventing CX3CL1-mediated retention of activated myeloid cells at sites of injury.<\/jats:p>","DOI":"10.1038\/s41419-021-03423-2","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T10:05:38Z","timestamp":1612433138000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inhibition of mPGES-1 attenuates efficient resolution of acute inflammation by enhancing CX3CL1 expression"],"prefix":"10.1038","volume":"12","author":[{"given":"Peter","family":"Rappl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"R\u00f6sser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Maul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9799-7489","authenticated-orcid":false,"given":"Rebekka","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Huard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannick","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Geisslinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per-Johan","family":"Jakobsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-1952","authenticated-orcid":false,"given":"Andreas","family":"Weigert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8237-2841","authenticated-orcid":false,"given":"Bernhard","family":"Br\u00fcne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-5259","authenticated-orcid":false,"given":"Tobias","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"3423_CR1","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1084\/jem.185.2.207","volume":"185","author":"DE Morgenstern","year":"1997","unstructured":"Morgenstern, D. 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