Hypoxia-reoxygenation enhances interleukin-8 production from U937 human monocytic cells

Redox Rep. 2004;9(6):365-9. doi: 10.1179/135100004225006894.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia / physiology*
  • Humans
  • I-kappa B Proteins / genetics
  • Interleukin-8 / biosynthesis*
  • Monocytes / immunology*
  • Monocytes / physiology
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / physiology
  • Oligopeptides / pharmacology
  • Oxygen / administration & dosage
  • Oxygen / pharmacology*
  • PPAR gamma / agonists
  • Pioglitazone
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology
  • Thiazolidinediones / pharmacology
  • Transfection
  • U937 Cells

Substances

  • 15-deoxyprostaglandin J2
  • I-kappa B Proteins
  • Interleukin-8
  • NF-kappa B
  • NFKBIA protein, human
  • Oligopeptides
  • PPAR gamma
  • Thiazolidinediones
  • benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal
  • NF-KappaB Inhibitor alpha
  • Prostaglandin D2
  • Oxygen
  • Pioglitazone