Sökning: WFRF:(Weigert A) > Inhibition of mPGES...
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000 | 02953naa a2200397 4500 | |
001 | oai:prod.swepub.kib.ki.se:147247316 | |
003 | SwePub | |
008 | 240811s2021 | |||||||||||000 ||eng| | |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1472473162 URI |
024 | 7 | a https://doi.org/10.1038/s41419-021-03423-22 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Rappl, P4 aut |
245 | 1 0 | a Inhibition of mPGES-1 attenuates efficient resolution of acute inflammation by enhancing CX3CL1 expression |
264 | c 2021-02-02 | |
264 | 1 | b Springer Science and Business Media LLC,c 2021 |
520 | a Despite the progress to understand inflammatory reactions, mechanisms causing their resolution remain poorly understood. Prostanoids, especially prostaglandin E2 (PGE2), are well-characterized mediators of inflammation. PGE2 is produced in an inducible manner in macrophages (Mϕ) by microsomal PGE2-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 PGE2-blocking efficacy. mPGES-1 inhibition resulted in an incomplete removal of neutrophils and a concomitant increase in monocytes and Mϕ during the resolution process. The mRNA-seq analysis identified enhanced C-X3-C motif receptor 1 (CX3CR1) expression in resident and infiltrating Mϕ upon mPGES-1 inhibition. Besides elevated Cx3cr1 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 Mϕ 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 PGE2 contributes to the resolution of inflammation by preventing CX3CL1-mediated retention of activated myeloid cells at sites of injury. | |
700 | 1 | a Rosser, S4 aut |
700 | 1 | a Maul, P4 aut |
700 | 1 | a Bauer, R4 aut |
700 | 1 | a Huard, A4 aut |
700 | 1 | a Schreiber, Y4 aut |
700 | 1 | a Thomas, D4 aut |
700 | 1 | a Geisslinger, G4 aut |
700 | 1 | a Jakobsson, PJu Karolinska Institutet4 aut |
700 | 1 | a Weigert, A4 aut |
700 | 1 | a Brune, B4 aut |
700 | 1 | a Schmid, T4 aut |
710 | 2 | a Karolinska Institutet4 org |
773 | 0 | t Cell death & diseased : Springer Science and Business Media LLCg 12:2, s. 135-q 12:2<135-x 2041-4889 |
856 | 4 | u https://www.nature.com/articles/s41419-021-03423-2.pdf |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:147247316 |
856 | 4 8 | u https://doi.org/10.1038/s41419-021-03423-2 |
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