Cytokine-activated degradation of inhibitory κB protein α is inhibited by the short-chain fatty acid butyrate
Cytokine-activated degradation of inhibitory κB protein α is inhibited by the short-chain fatty acid butyrate
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DOI：
10.1007/s003840100295
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发表时间：
2001-08-01
影响因子：
2.8
通讯作者：
Menzel, T
中科院分区：
文献类型：
--
作者：
Lührs, H;Gerke, T;Menzel, T
丁酸是一种短链脂肪酸，通过结肠内的厌氧发酵产生。临床试验表明，短链脂肪酸可改善溃疡性结肠炎的炎症。核因子（NF）kappaB是一种在发炎的结肠组织中被激活的诱导型转录因子，通过其抑制性I kappaB蛋白被隔离到细胞质中。丁酸盐的抗炎作用与抑制NF-κ B核转位有关。为了研究NF-κ B抑制的机制，我们检测了丁酸盐对I κ B α的影响。用丁酸盐处理人腺癌细胞（SW 480、SW 620和HeLa 229）长达48 h，然后进行肿瘤坏死因子（TNF）α刺激。NF-κ B的检测通过免疫荧光染色与其p65亚基的抗体。通过蛋白质印迹法测定I κ B α和磷酸化I κ B α的水平。用TNF α刺激导致I κ B α快速磷酸化和降解，随后是NF-κ B核转位。丁酸盐预处理成功地抑制了NF-κ B活化。用丁酸盐预处理腺癌细胞与抑制TNF α介导的磷酸化和I κ B α降解以及有效阻断NF-κ B核转位相关。丁酸盐的抗炎作用可以至少部分地通过抑制I κ B α介导的NF-κ B活化来介导。
Butyrate, a short-chain fatty acid, is generated by anaerobic fermentation within the colon. Clinical trials suggest that short-chain fatty acids ameliorate inflammation in ulcerative colitis. Nuclear factor (NF) kappaB, an inducible transcription factor that is activated in inflamed colonic tissue, is sequestered to the cytoplasm by its inhibitory I kappaB proteins. The anti-inflammatory effects of butyrate are associated with an inhibition of NF-kappaB nuclear translocation. To investigate the mechanism of NF-kappaB inhibition we examined the effects of butyrate on I kappaB alpha. Human adenocarcinoma cells (SW480, SW620, and HeLa229) were treated with butyrate for up to 48 h followed by tumor necrosis factor (TNF) alpha stimulation. NF-kappaB was detected by immunofluorescence staining with an antibody against its p65 subunit. Levels of I kappaB alpha and phosphorylated I kappaB alpha were determined by western blot. Stimulation with TNF alpha resulted in rapid phosphorylation and degradation of I kappaB alpha followed by NF-kappaB nuclear translocation. Butyrate pretreatment successfully inhibited NF-kappaB activation. Pretreatment of adenocarcinoma cells with butyrate is associated with inhibition of TNF alpha -mediated phosphorylation and degradation of I kappaB alpha and effective blocking of NF-kappaB nuclear translocation. The anti-inflammatory effects of butyrate may at least in part be mediated by an inhibition of I kappaB alpha mediated activation of NF-kappaB.