Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis
Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis
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DOI：
10.1007/s11010-014-2162-8
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发表时间：
2014-11-01
影响因子：
4.3
通讯作者：
Suguna, Periyanayagam
中科院分区：
文献类型：
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作者：
Aruna, Ravikumar;Geetha, Arumugam;Suguna, Periyanayagam
炎性小体是响应于组织损伤和炎症而形成的蛋白质复合物，以调节促炎细胞因子的形成。Nod-like receptor pyrin domain containing 3（NLRP 3）是一种参与胰腺炎症的炎性小体。半胱天冬酶激活募集结构域（CARD）是在NLRP 3炎性小体的所有主要组分中发现的相互作用基序，例如凋亡相关的含斑点样CARD蛋白（ASC）和半胱天冬酶原-1。NLRP 3通过ASC的CARD结构域的协同作用激活procaspase-1。在本研究中，芦丁，一种天然黄酮对NLRP 3的ASC表达的影响，在用乙醇（EtOH）和雨蛙素（Cer）处理的大鼠中进行了研究。将雄性白化病Wistar大鼠分为4组。给第1组和第2组大鼠喂食正常饮食，而给第3组和第4组大鼠喂食含有EtOH（总热量的36%）的饮食总共5周，并且还施用Cer（20 μ g/kg体重，i. p.）过去三周每周三次此外，第2组和第4组大鼠从第三周开始每天接受100 mg/kg体重的芦丁。在接受EtOH-Cer的大鼠中，RbR联合给药显著降低胰腺标志酶、氧化应激标志物、炎症标志物、caspase-1、细胞因子、ASC-NLRP 3的mRNA表达以及caspase-1和ASC的蛋白表达水平。研究结果表明，芦丁可能通过影响ASC-NLRP 3的下调，从而减少caspase-1的活化和控制细胞因子的产生，从而减轻胰腺炎症。
Inflammasomes are protein complexes formed in response to tissue injury and inflammation to regulate the formation of proinflammatory cytokines. Nod-like receptor pyrin domain containing 3 (NLRP3) is one such inflammasome involved in pancreatic inflammation. Caspase activation recruitment domain (CARD) is an interaction motif found in all the major components of NLRP3 inflammasome such as apoptosis associated speck-like CARD containing protein (ASC) and procaspase-1. NLRP3 activates procaspase-1 with the concerted action of CARD domain of ASC. In the present study, the effect of rutin, a natural flavonoid on the expression of ASC of NLRP3, was investigated in rats treated with ethanol (EtOH) and cerulein (Cer). Male albino Wistar rats were divided into four groups. Groups 1 and 2 rats were fed normal diet, whereas groups 3 and 4 rats were fed EtOH (36 % of total calories) containing diet for a total period of 5 weeks and also administered Cer (20 A mu g/kg body weight i.p.) thrice weekly for the last 3 weeks. In addition, groups 2 and 4 rats received daily 100 mg/kg body weight of rutin from third week. Rutin co-administration significantly decreased the level of pancreatic marker enzymes, oxidative stress markers, inflammatory markers, mRNA expression of caspase-1, cytokines, ASC-NLRP3, and protein expression of caspase-1 and ASC in rats received EtOH-Cer. The results of the study revealed that rutin can reduce inflammation in pancreas probably by influencing the down regulation of ASC-NLRP3 which might result in the reduced activation of caspase-1 and controlled cytokine production.