title: Dual Roles of Group IID Phospholipase A2 in Inflammation and Cancer.
abstract: Phospholipase A2 enzymes have long been implicated in the promotion of inflammation by mobilizing pro-inflammatory lipid mediators, yet recent evidence suggests that they also contribute to anti-inflammatory or pro-resolving programs. Group IID-secreted phospholipase A2 (sPLA2-IID) is abundantly expressed in dendritic cells in lymphoid tissues and resolves the Th1 immune response by controlling the steady-state levels of anti-inflammatory lipids such as docosahexaenoic acid and its metabolites. Here, we show that psoriasis and contact dermatitis were exacerbated in Pla2g2d-null mice, whereas they were ameliorated in Pla2g2d-overexpressing transgenic mice, relative to littermate wild-type mice. These phenotypes were associated with concomitant alterations in the tissue levels of ω3 polyunsaturated fatty acid (PUFA) metabolites, which had the capacity to reduce the expression of pro-inflammatory and Th1/Th17-type cytokines in dendritic cells or lymph node cells. In the context of cancer, however, Pla2g2d deficiency resulted in marked attenuation of skin carcinogenesis, likely because of the augmented anti-tumor immunity. Altogether, these results underscore a general role of sPLA2-IID as an immunosuppressive sPLA2 that allows the microenvironmental lipid balance toward an anti-inflammatory state, exerting beneficial or detrimental impact depending upon distinct pathophysiological contexts in inflammation and cancer.
authors.affiliation: From the Lipid Metabolism Project and.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Miki
authors.affiliation: From the Lipid Metabolism Project and the School of Science and Engineering, Tokyo Denki University, Saitama 350-0394, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Kidoguchi
authors.affiliation: From the Lipid Metabolism Project and the School of Science and Engineering, Tokyo Denki University, Saitama 350-0394, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sato
authors.affiliation: From the Lipid Metabolism Project and.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taketomi
authors.affiliation: Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.affiliation: the School of Science and Engineering, Tokyo Denki University, Saitama 350-0394, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Muramatsu
authors.affiliation: the Departments of Chemistry and Biochemistry, University of Washington, Seattle, Washington 98195.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.affiliation: From the Lipid Metabolism Project and the Faculty of Bioscience and Bioindustry, Tokushima University, Tokushima 770-8513, Japan, and PRIME and.
authors.forename: Kei
authors.initials: K
authors.lastname: Yamamoto
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; D015525:Fatty Acids, Omega-3 / Q000235:genetics / Q000276:immunology; D054501:Group II Phospholipases A2 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D015525:Fatty Acids, Omega-3; D009363:Neoplasm Proteins; D054501:Group II Phospholipases A2; C516294:Pla2g2d protein, mouse