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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00002953naa a2200397 4500
001oai:prod.swepub.kib.ki.se:147247316
003SwePub
008240811s2021 | |||||||||||000 ||eng|
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:1472473162 URI
024a https://doi.org/10.1038/s41419-021-03423-22 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Rappl, P4 aut
2451 0a Inhibition of mPGES-1 attenuates efficient resolution of acute inflammation by enhancing CX3CL1 expression
264 c 2021-02-02
264 1b 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.
700a Rosser, S4 aut
700a Maul, P4 aut
700a Bauer, R4 aut
700a Huard, A4 aut
700a Schreiber, Y4 aut
700a Thomas, D4 aut
700a Geisslinger, G4 aut
700a Jakobsson, PJu Karolinska Institutet4 aut
700a Weigert, A4 aut
700a Brune, B4 aut
700a Schmid, T4 aut
710a Karolinska Institutet4 org
773t Cell death & diseased : Springer Science and Business Media LLCg 12:2, s. 135-q 12:2<135-x 2041-4889
856u https://www.nature.com/articles/s41419-021-03423-2.pdf
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:147247316
8564 8u https://doi.org/10.1038/s41419-021-03423-2

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