Differential roles of hydrogen peroxide and superoxide in mediating IL‐1‐induced NF‐κB activation and iNOS expression in bovine articular chondrocytes

Abstract

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.

Increased mitochondrial biogenesis in primary leukemia cells: the role of endogenous nitric oxide and impact on sensitivity to fludarabine

“…3,4,30,31 Additionally, these studies shed new light on a potential consequence of oxidative and nitrosative stress, which has been reported in many tumor types. Our findings provide evidence directly obtained from clinical specimens implicating the important role of nitric oxide in mitochondrial biogenesis in primary malignant cells.…”

Nuclear Heat Shock Protein 72 as a Negative Regulator of Oxidative Stress (Hydrogen Peroxide)-Induced HMGB1 Cytoplasmic Translocation and Release

“…O xidative stress is caused by excessive accumulation of reactive oxygen species (ROS) 4 as a result of a defective antioxidant defense system of the cell, and has been implicated in a variety of pathophysiological conditions including inflammation and the aging process (1)(2)(3). An increase in intracellular ROS levels can lead to cell damages via lipid peroxidation, protein cross-linkage, and DNA breakage.…”

Hyperglycemia and Hyperinsulinemia-Like Conditions Independently Induce Inflammatory Responses in Human Chondrocytes

“…Taking these studies together, it seems likely that high glucose-induced NF-κB activation can result, at least in part, from the increased production of ROS elicited by the intracellular glucose accumulation observed in aged/OA chondrocytes exposed to high glucose [11]. The observation that the selective inhibitor of the canonical NF-κB activation pathway, Bay 11-7082, completely abrogated high glucose-induced NF-κB activation shows that the response to high glucose occurs through this pathway and further supports a possible role for ROS, since these have been shown to be required for IL-1β-induced IκB-α degradation in chondrocytes [18,25]. Further studies will be directed at confirming this association and evaluating the efficacy of antioxidants in preventing high glucose-induced NF-κB activation and the expression of its dependent genes.…”

“…since these have been shown to be required for IL-1β-induced IκB-α degradation in chondrocytes [18,25]. Further studies will be directed at confirming this association and evaluating the efficacy of antioxidants in preventing high glucose-induced NF-κB activation and the expression of its dependent genes.…”

“…The rapid nuclear translocation of p65 induced by high glucose suggests a direct effect on the NF-κB signaling pathway in chondrocytes. In a previous study, we reported that culture of human aged/OA chondrocytes under high glucose elicits the prolonged production of reactive oxygen species (ROS) [11], which were shown to mediate IL-1β-induced NF-κB activation and the expression of iNOS in chondrocytes [25]. Taking these studies together, it seems likely that high glucose-induced NF-κB activation can result, at least in part, from the increased production of ROS elicited by the intracellular glucose accumulation observed in aged/OA chondrocytes exposed to high glucose [11].…”