title: Trans fatty acids exacerbate dextran sodium sulphate-induced colitis by promoting the up-regulation of macrophage-derived proinflammatory cytokines involved in T helper 17 cell polarization.
abstract: Numerous reports have shown that a diet containing large amounts of trans fatty acids (TFAs) is a major risk factor for metabolic disorders. Although recent studies have shown that TFAs promote intestinal inflammation, the underlying mechanisms are unknown. In this study, we examined the effects of dietary fat containing TFAs on dextran sodium sulphate (DSS)-induced colitis. C57 BL/6 mice were fed a diet containing 1·3% TFAs (mainly C16:1, C18:1, C18:2, C20:1, C20:2 and C22:1), and then colitis was induced with 1·5% DSS. Colonic damage was assessed, and the mRNA levels of proinflammatory cytokines and major regulators of T cell differentiation were measured. The TFA diet reduced survival and exacerbated histological damage in mice administered DSS compared with those fed a TFA-free diet. The TFA diet significantly elevated interleukin (IL)-6, IL-12p40, IL-23p19 and retinoic acid-related orphan receptor (ROR)γt mRNA levels in the colons of DSS-treated animals. Moreover, IL-17A mRNA levels were elevated significantly by the TFA diet, with or without DSS treatment. We also examined the expression of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and peritoneal macrophages. These cells were exposed to TFAs (linoelaidic acid or elaidic acid) with or without LPS and the mRNA levels of various cytokines were measured. IL-23p19 mRNA levels were increased significantly by TFAs in the absence of LPS. Cytokine expression was also higher in LPS-stimulated cells exposed to TFAs than in unexposed LPS-stimulated cells. Collectively, our results suggest that TFAs exacerbate colonic inflammation by promoting Th17 polarization and by up-regulating the expression of proinflammatory cytokines in the inflamed colonic mucosa.
authors.affiliation: Department of Internal Medicine, National Defense Medical College, Tokorozawa City, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuzuki
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Narimatsu
authors.forename: R
authors.initials: R
authors.lastname: Hokari
authors.forename: C
authors.initials: C
authors.lastname: Kurihara
authors.forename: C
authors.initials: C
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Tomita
authors.forename: S
authors.initials: S
authors.lastname: Komoto
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: S
authors.initials: S
authors.lastname: Nagao
authors.forename: S
authors.initials: S
authors.lastname: Miura
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D016264:Dextran Sulfate; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D019787:Linoleic Acid; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000235:genetics; D019301:Oleic Acid; D009829:Oleic Acids; D012333:RNA, Messenger / Q000096:biosynthesis; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D044242:Trans Fatty Acids; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C098680:Il17a protein, mouse; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; D008070:Lipopolysaccharides; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D009829:Oleic Acids; D012333:RNA, Messenger; D044242:Trans Fatty Acids; D019301:Oleic Acid; C011459:elaidic acid; D016264:Dextran Sulfate; D019787:Linoleic Acid
keywords: inflammatory bowel disease; macrophages; proinflammatory cytokines; trans fatty acids
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