Differential roles of hydrogen peroxide and superoxide in mediating IL-1-induced NF-kappa B activation and iNOS expression in bovine articular chondrocytes.
Our previous studies showed that reactive oxygen species (ROS) are required for the pro-inflammatory cytokine interleukin-1 beta (IL-1) to induce the activity of the Nuclear transcription Factor-kappa B (NF-kappa B) and the expression of the inducible isoform of the nitric oxide synthase (iNOS) in bovine articular chondrocytes. This study aimed at elucidating the role of hydrogen peroxide (H(2)O(2)) and the superoxide radical, two major ROS, in mediating those IL-1-induced responses. The results obtained show that chondrocytes produce both H(2)O(2) and superoxide radical in response to IL-1. Treatment of the chondrocyte cultures with H(2)O(2) alone did not induce NF-kappa B activation or iNOS expression. Addition of H(2)O(2) simultaneously with IL-1 did neither enhance nor inhibit NF-kappa B activation and iNOS expression, relatively to treatment with IL-1 alone. Accordingly, treatment with catalase did not inhibit those IL-1-induced responses. Treatment with superoxide dismutase, however, effectively prevented IL-1-induced I kappa B-alpha degradation and iNOS expression. Taken together, the results obtained indicate that superoxide mediates IL-1-induced I kappa B-alpha degradation and the consequent NF-kappa B activation and iNOS expression in chondrocytes, whereas H(2)O(2) does not seem to participate in those IL-1-induced responses. In conclusion, the present study identifies the superoxide radical as the ROS involved in mediating the IL-1-induced signaling pathway that leads to NF-kappa B activation and to the expression of NF-kappa B-dependent genes in bovine articular chondrocytes.
Mendes
Alexandrina Ferreira
AF
Faculty of Pharmacy and Centre for Neurosciences of Coimbra, Department of Zoology, , University of Coimbra, Portugal. alexandrinam@hotmail.com
Caramona
M Margarida
MM
Carvalho
A Pato
AP
Lopes
M Celeste
MC
D000818:Animals; D002358:Cartilage, Articular; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism* / Q000494:pharmacology
D007375:Interleukin-1; D016328:NF-kappa B; D013481:Superoxides; D006861:Hydrogen Peroxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase