title: Regulation by interleukin-10 and interleukin-4 of cyclooxygenase-2 expression in human neutrophils.
abstract: Neutrophils are important effector cells of acute inflammation because of their potential capacity to synthesize various proinflammatory mediators, and inhibition of their production is expected to result in anti-inflammatory effects. In this study, we investigate the effects of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, on prostanoid synthesis in human neutrophils. Neutrophils isolated from healthy donors constitutively produced a small amount of prostaglandin E2 (PGE2) without any stimulations, whereas they produced a large amount of PGE2 after lipopolysaccharide (LPS) stimulation. IL-10 and IL-4 selectively inhibited their LPS-induced PGE2 production. Inhibition by both cytokines occurred at an early stage of LPS stimulation. Anti-IL-10 treatment of LPS-stimulated neutrophils resulted in enhanced PGE2 production. LPS-induced PGE2 and thromboxane B2 (TXB2) production in aspirin-treated neutrophils was significantly inhibited by IL-10, IL-4, and NS-398. Moreover, IL-10 and IL-4 inhibited LPS-induced cyclooxygenase (COX) activity in neutrophils. Western blot and immunocytochemical analysis showed that COX-2 protein was clearly induced in LPS-stimulated neutrophils and that its induction was inhibited by both IL-10 and IL-4. Moreover, both of these cytokines inhibited COX-2 mRNA expression in LPS-stimulated neutrophils. These results raise the possibility that these two cytokines may both offer potent clinical utility as anti-inflammatory agents in the future.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Niiro
authors.forename: T
authors.initials: T
authors.lastname: Otsuka
authors.forename: K
authors.initials: K
authors.lastname: Izuhara
authors.forename: K
authors.initials: K
authors.lastname: Yamaoka
authors.forename: K
authors.initials: K
authors.lastname: Ohshima
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Nemoto
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases