title: Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility.
abstract: Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizerin vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization.
authors.affiliation: From the Lipid Metabolism Project and School of Pharmacy, Showa University, Tokyo 142-8555, Japan.
authors.forename: Remi
authors.initials: R
authors.lastname: Murase
authors.affiliation: From the Lipid Metabolism Project and.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.affiliation: From the Lipid Metabolism Project and PRIME and.
authors.forename: Kei
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: From the Lipid Metabolism Project and Department of Biology, Faculty of Science, Ochanomizu University, Tokyo 112-8610, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ushida
authors.affiliation: Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishito
authors.affiliation: Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan, and.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Department of Biology, Faculty of Science, Ochanomizu University, Tokyo 112-8610, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: School of Pharmacy, Showa University, Tokyo 142-8555, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: From the Lipid Metabolism Project and.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taketomi
authors.affiliation: From the Lipid Metabolism Project and AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan murakami-mk@igakuken.or.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D016264:Dextran Sulfate; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis* / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000096:biosynthesis / Q000378:metabolism; D005298:Fertility / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D054509:Group X Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000201:enzymology* / Q000473:pathology; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology; D019076:Transgenes
chemical_list: C498007:FFAR4 protein, mouse; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D020381:Interleukin-17; D043562:Receptors, G-Protein-Coupled; D016718:Arachidonic Acid; D016264:Dextran Sulfate; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; D054467:Phospholipases A2
keywords: Phospholipase A; arachidonic acid (AA) (ARA); colitis; inflammation; lipid metabolism; membrane; polyunsaturated fatty acid (PUFA); prostaglandin; sperm
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