title: Cellular basis of the role of diesel exhaust particles in inducing Th2-dominant response.
abstract: There is growing evidence that diesel exhaust particles (DEP) can induce allergic diseases with increased IgE production and preferential activation of Th2 cells. To clarify the cellular basis of the role of DEP in the induction of Th2-dominant responses, we examined the effects of DEP on the cytokine production by T cells stimulated with anti-CD3/CD28 Ab and on that by monocyte-derived dendritic cells (MoDCs) stimulated with CD40L and/or IFN-gamma. We examined IFN-gamma, IL-4, IL-5, IL-8, and IL-10 produced by T cells and TNF-alpha, IL-1beta, IL-10, and IL-12 produced by MoDCs using real-time PCR analysis or by ELISA. To highlight the effects of DEP, we compared the effects of DEP with those of dexamethasone (DEX) and cyclosporin A (CyA). DEP significantly suppressed IFN-gamma mRNA expression and protein production, while it did not affect IL-4 or IL-5 mRNA expression or protein production. The suppressive effect on IFN-gamma mRNA expression was more potent than that of DEX and comparable at 30 mug/ml with 10(-7) M CyA. The suppressive effect on IFN-gamma production was also more potent than that of either DEX or CyA. DEP suppressed IL-12p40 and IL-12p35 mRNA expression and IL-12p40 and IL-12p70 production by MoDCs, while it augmented IL-1beta mRNA expression. Finally, by using a thiol antioxidant, N-acetyl cysteine, we found that the suppression of IFN-gamma production by DEP-treated T cells was mediated by oxidative stress. These data revealed a unique characteristic of DEP, namely that they induce a Th2 cytokine milieu in both T cells and dendritic cells.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohtani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosawa
authors.forename: Masato
authors.initials: M
authors.lastname: Mizuashi
authors.forename: Maki
authors.initials: M
authors.lastname: Ozawa
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D000393:Air Pollutants / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000633:toxicity; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D012333:RNA, Messenger; D001335:Vehicle Emissions; D016753:Interleukin-10; D007371:Interferon-gamma; D002392:Catechin; C045651:epigallocatechin gallate; D000111:Acetylcysteine