Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages
Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages
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DOI：
10.1016/j.cyto.2006.11.003
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发表时间：
2006-11-01
期刊：
影响因子：
3.8
通讯作者：
Srivastava, Satish K.
中科院分区：
文献类型：
--
作者：
Ramana, Kota V.;Srivastava, Satish K.
醛糖还原酶（AR; AKR 1B 1是醛酮还原酶超家族的成员，在高糖、细胞因子和生长因子诱导的细胞毒信号中起重要作用，也参与了革兰氏阴性细菌内毒素、脂多糖（LPS）诱导的炎症信号的调节。通过三种不同的AR抑制剂sorbinil、tolrestat或zopolrestat抑制AR抑制LPS诱导的炎性细胞因子如TNF-α、IL-6、IL-1 β、IFN-γ和趋化因子MCP-1在小鼠腹腔巨噬细胞中的产生。AR的抑制也阻止了一氧化氮和前列腺素E2的产生以及iNOS和考克斯-2蛋白的表达。AR抑制剂可显著抑制LPS诱导的NF-κ B B和AP 1的DNA结合活性，这种作用是通过抑制I κ B-α、IKK α/β和PKC的磷酸化而介导的。这些结果表明AR抑制剂作为抗炎药的治疗用途。(c)2006爱思唯尔有限公司保留所有权利。
Aldose reductase (AR; AKR1B1) a member of aldo-keto reductase super family, that we had shown earlier mediates cytotoxic signals induced by high glucose, cytokines and growth factors, also mediates the inflammatory signals induced by Gram-negative bacterial endotoxin, lipopolysaccharide (LPS). Inhibition of AR by three distinct AR inhibitors sorbinil, tolrestat or zopolrestat suppressed the LPS-induced production of inflammatory cytokines such as TNF-alpha, IL-6, IL-1 beta, IFN-gamma, and chemokine MCP-1 in murine peritoneal macrophages. Inhibition of AR also prevented the production of nitric oxide, and prostaglandin E2 and expression of iNOS and Cox-2 proteins. The LPS-induced DNA binding activity of NF-kappa B and AP1 were significantly inhibited by AR inhibitors, and this effect was mediated through the inhibition of phosphorylation of I kappa B-alpha, IKK alpha/beta and PKC. These results suggest the therapeutic use of AR inhibitors as anti-inflammatory drugs. (c) 2006 Elsevier Ltd. All rights reserved.