Hypoxia/reoxygenation stimulates endothelial cells to promote interleukin-1 and interleukin-6 production. Effects of free radical scavengers.
Vascular endothelium produces and/or interferes with various cytokines. Previous studies have demonstrated interactions of these inflammatory and immunological mediators with oxygen-derived free radicals. The present work examines the relationship between hypoxia/reoxygenation (H/R) and cytokine production by cultured endothelial cells. Human umbilical vein endothelial cell (HUVEC) monolayers were incubated for 24 h in normoxia or submitted to 5 h hypoxia/19 h reoxygenation. Then, interleukin-1 (IL-1) alpha and beta, and interleukin-6 (IL-6), were measured in culture supernatants by specific enzyme immunoassays and bioassays, respectively. Under these conditions, the spontaneous production of IL-1 and IL-6, detected in normoxic HUVEC, greatly increased after H/R treatment. The observed enhancement was cycloheximide-sensitive and, consequently, reflected a de novo protein synthesis. Superoxide dismutase and glutathione peroxidase prevented H/R-induced IL-1 and IL-6 increase. These results constitute the first demonstration that H/R stimulates HUVEC to promote IL-1 and IL-6 production and strongly suggest a role for oxygen-derived free radicals in the cytokine synthesis.
Ala
Y
Y
Laboratoire de physiologie cellulaire, Faculté de Pharmacie, Université de Montpellier I, France.
Palluy
O
O
Favero
J
J
Bonne
C
C
Modat
G
G
Dornand
J
J
D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016166:Free Radical Scavengers; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D010101:Oxygen Consumption / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism
D016166:Free Radical Scavengers; D005609:Free Radicals; D007375:Interleukin-1; D015850:Interleukin-6; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase