title: Glucocorticoids inhibit chemokine generation by human eosinophils.
abstract: Recent identification of eosinophils as a cellular source of various cytokines suggests that eosinophil-derived cytokines contribute to allergic inflammation through either an autocrine or a paracrine fashion. The profound inhibitory effects of glucocorticoids (GCCs) on the production of various cytokines have been well recognized, however, there has been no definitive evidence that GCCs in fact inhibit cytokine generation by eosinophils. To verify the inhibitory ability of GCCs on eosinophil cytokine generation, we studied the effect of GCCs by determination of IL-8 and monocyte chemoattractant protein-1 (MCP-1) as parameters. Dexamethasone (DEX) inhibited both generation and secretion of IL-8 in a dose-dependent fashion. DEX also dampened formyl-methionyl-leucyl-phenylalanine-or ionomycin-induced eosinophil IL-8 production. Furthermore, MCP-1 production was also inhibited by DEX. The slope and the shape of the dose-response curve of DEX were similar irrespective of either the input stimuli or the output cytokines; half-maximal inhibition was observed at 10(-8) mol/L, and nearly complete abolishment was observed at 10(-7) mol/L. The competitive polymerase chain reaction for IL-8 mRNA and semiquantitative polymerase chain reaction for MCP-1 mRNA revealed that the inhibition occurred at a level of pretranslation. These results indicate that the beneficial effect of GCCs in allergic inflammation might be related, at least in part, to a direct effect of the drugs on eosinophil cytokine synthesis.
authors.affiliation: Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyamasu
authors.forename: Y
authors.initials: Y
authors.lastname: Misaki
authors.forename: S
authors.initials: S
authors.lastname: Izumi
authors.forename: T
authors.initials: T
authors.lastname: Takaishi
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: T
authors.initials: T
authors.lastname: Kasahara
authors.forename: K
authors.initials: K
authors.lastname: Hirai
mesh_terms: D001483:Base Sequence; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D015936:Complement C5a / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D008775:Methylprednisolone / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D017931:DNA Primers; D005938:Glucocorticoids; D016209:Interleukin-8; D012333:RNA, Messenger; D013256:Steroids; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003907:Dexamethasone; D015936:Complement C5a; D006854:Hydrocortisone; D008775:Methylprednisolone