title: Oxidative injury amplifies interleukin-1-like activity produced by human monocytes.
abstract: Exposure of human monocytes to 95% normobaric oxygen (O2) was used as an in vitro oxidative injury model to study the effects of the O2-derived species produced by phagocytes at inflammatory sites on monocyte IL-1 production. Exposure to O2 enhanced production by monocytes of IL-1-like activity whether the adherent cells were cultured in the presence of opsonized zymosan, LPS or medium alone. This O2-induced increase in production of IL-1 activity was inhibited by cycloheximide and thus resulted from de novo protein synthesis. Furthermore, the increase was prevented by the addition of the protein kinase inhibitor N-2-methylaminoethyl-5-isoquinoline sulfonamide dihydrochloride (H8). Following exposure to O2, Ca2+/phospholipid-independent protein kinase activity increased in comparison to air-exposed monocytes, whereas the dependent form decreased. Since the Ca2+/phospholipid-independent form is known to derive from the dependent form (protein kinase C) by proteolysis in the presence of a thiol proteinase, our results suggest that oxidative injury stimulates thiol proteinase activity and enhances production of IL-1 activity by human monocytes partly by interfering with protein kinase C metabolism. Among the consequences of the generation of O2-derived species by phagocytes in inflammatory sites, the augmentation of the production of IL-1-like activity could amplify the inflammatory response.
authors.affiliation: INSERM U. 294, Chu Bichat, Paris, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.forename: Y
authors.initials: Y
authors.lastname: Roche
authors.forename: M
authors.initials: M
authors.lastname: Fay
authors.forename: A
authors.initials: A
authors.lastname: Perianin
authors.forename: S
authors.initials: S
authors.lastname: Bailly
mesh_terms: D000328:Adult; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D007546:Isoquinolines; D008070:Lipopolysaccharides; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D015054:Zymosan; D003513:Cycloheximide; D011493:Protein Kinase C; D010100:Oxygen