title: IL-1 beta protects human chondrocytes from CD95-induced apoptosis.
abstract: This study addresses the effects of IL-1 beta on apoptosis induced by agonistic anti-CD95 (Fas) Ab. IL-1 beta inhibited anti-CD95 Ab-induced apoptosis in all preparations of normal human articular chondrocytes tested. Inhibitors of nitric oxide synthase or cyclooxygenase did not influence the protective effect of IL-1 beta, indicating that nitric oxide and PGs were not involved in the modulation of CD95-induced apoptosis. However, when the IL-1 beta-dependent induction of NF-kappa B was inhibited, the antiapoptotic effect of IL-1 beta was partially reversed, suggesting that NF-kappa B-mediated gene activation is part of the protective mechanism. In addition, IL-1 beta significantly increased the expression of Bcl-2. The protein tyrosine kinase inhibitor herbimycin A completely eliminated the protective effect of IL-1 beta on CD95-induced apoptosis. These findings suggest that IL-1 beta modulates the CD95 death cascade in chondrocytes by mechanisms that involve tyrosine phosphorylation events and NF-kappa B-dependent gene activation.
authors.affiliation: Division of Arthritis Research, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kühn
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Lotz
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D009569:Nitric Oxide; D014443:Tyrosine