title: Hypoxia-reoxygenation enhances interleukin-8 production from U937 human monocytic cells.
abstract: Hypoxia--reoxygenation (H/R) occurs in both inflammatory spots and tumor tissues, sites in which damage is amplified either acutely or chronically through the infiltration of inflammatory cells. Interleukin-8 (IL-8) is a cytokine with chemotactic and angiogenic properties. This study was designed to investigate the effects of H/R on IL-8 production in the U937 human monocytic cell line. Two hours of hypoxia followed by 4 h of reoxygenation induced a significant increase in IL-8 protein production and IL-8 mRNA expression in U937 cells. Pretreatment with proteasome inhibitor (PSI), a peptide aldehyde known to inhibit the chymotrypsin-like activity of the 26S proteasome specifically, suppressed IL-8 protein production and IL-8 mRNA expression induced by H/R. The production of IL-8 protein induced by H/R was decreased by pioglitazone and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)), which have been identified as peroxisome proliferator-activated receptorgamma (PPAR-gamma) ligands. Moreover, transfection of U937 cells with a dominant negative IkappaBalphaexpression vector (IkappaBalphaM) decreased IL-8 protein production induced by H/R. These results suggest that NF-kappaB and PPAR-gamma regulate H/R-stimulated IL-8 production in U937 cells.
authors.affiliation: Departments of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Higashihara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Eiko
authors.initials: E
authors.lastname: Imamoto
authors.forename: Miho
authors.initials: M
authors.lastname: Ueda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D014162:Transfection; D020298:U937 Cells
chemical_list: C477819:15-deoxyprostaglandin J2; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D009842:Oligopeptides; D047495:PPAR gamma; D045162:Thiazolidinediones; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D000072000:NF-KappaB Inhibitor alpha; D015230:Prostaglandin D2; D010100:Oxygen; D000077205:Pioglitazone