Differential roles of hydrogen peroxide and superoxide in mediating IL-1-induced NF-κB activation and iNOS expression in bovine articular chondrocytes
Differential roles of hydrogen peroxide and superoxide in mediating IL-1-induced NF-κB activation and iNOS expression in bovine articular chondrocytes
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DOI：
10.1002/jcb.10428
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发表时间：
2003-03-01
影响因子：
4
通讯作者：
Lopes, MC
中科院分区：
文献类型：
--
作者：
Mendes, AF;Caramona, MM;Lopes, MC
我们的前期研究表明，活性氧（ROS）是促炎因子白细胞介素-1 β（IL-1）诱导牛关节软骨细胞核转录因子-κ B（NF-κ B）活性和诱导型一氧化氮合酶（iNOS）表达所必需的。本研究旨在阐明过氧化氢（H2 O2）和超氧自由基，两个主要的活性氧，在介导这些IL-1诱导的反应的作用。结果表明，软骨细胞产生H2 O2和超氧自由基响应IL-1。单独用H2 O2处理软骨细胞培养物不诱导NF-κ B活化或iNOS表达。与单独IL-1处理相比，同时加入H2 O2和IL-1既不增强也不抑制NF-κ B活化和NOS表达。因此，用过氧化氢酶处理不抑制那些IL-1诱导的应答。然而，超氧化物歧化酶治疗有效地防止了IL-1诱导的IkappaB-α降解和NOS表达。两者合计，所获得的结果表明，超氧化物介导IL-1诱导的IkappaB-α降解和随后的NF-κ B激活和NOS在软骨细胞中的表达，而H2 O2似乎不参与这些IL-1诱导的反应。总之，本研究将超氧自由基确定为参与介导IL-1诱导的信号通路的活性氧，该信号通路导致牛关节软骨细胞中NF-κ B活化和NF-κ B依赖性基因的表达。
Our previous studies showed that reactive oxygen species (ROS) are required for the pro-inflammatory cytokineinterleukin-1beta (IL-1) to induce the activity of the Nuclear transcription Factor-kappaB (NF-kappaB) 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 (H2O2) and the superoxide radical, two major ROS, in mediating those IL-1 induced responses. The results obtained show that chondrocytes produce both H2O2 and superoxide radical in response to IL-1. Treatment of the chondrocyte cultures with H2O2 alone did not induce NF-kappaB activation or iNOS expression. Addition of H2O2 simultaneously with IL-1 did neither enhance nor inhibit NF-kappaB activation and NOS 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 IkappaB-alpha degradation and NOS expression. Taken together, the results obtained indicate that superoxide mediates IL-1-induced IkappaB-alpha degradation and the consequent NF-kappaB activation and NOS expression in chondrocytes, whereas H2O2 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-kappaB activation and to the expression of NF-kappaB-dependent genes in bovine articular chondrocytes.