Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells
Role of proinflammatory cytokines on expression of vitamin D metabolism and target genes in colon cancer cells
复制标题
DOI：
10.1016/j.jsbmb.2013.09.017
复制
发表时间：
2014-10-01
影响因子：
4.1
通讯作者：
Kallay, Eniko
中科院分区：
文献类型：
--
作者：
Hummel, Doris M.;Fetahu, Irfete S.;Kallay, Eniko
白介素6(IL-6)和肿瘤坏死因子α(TNFα)是促炎性细胞因子，在炎症性肠病和结直肠肿瘤的发生中起重要作用。我们假设这些细胞因子调节结肠上皮细胞中维生素D系统的表达和活性。我们用1，25-二羟基维生素D-3(1，25-D-3)、IL-6、TNFa及其组合作用于结肠癌细胞株COGA-1A 6、12和24小时。应用定量RT-PCR技术分析活化和分解1，25-D3基因(1α-羟基酶(CYP27B1)、24-羟基酶(CYP24A1))的mRNA表达，几个维生素D靶基因的表达，以及环氧合酶-2(COX-2)和15-羟基前列腺素脱氢酶(15-HPG)的表达。正如预期的那样，1，25-D3处理导致了细胞色素P24A1的表达上调，而细胞色素P27B1的表达没有受到影响。经TNFa和IL-6处理后，维生素D激活酶CYP27B1的表达下降。TNFa对COX-2的激活和对前列腺素E_2(PGE_2)分解代谢的抑制反映了TNFa的强炎性。有趣的是，钙离子通道TRPV6的表达被TNFa显著降低。根据这些结果，我们得出结论，致炎细胞因子的存在可能会削弱1，25-D3的激活，限制其抗炎作用。(C)2013年提交人。爱思唯尔有限公司出版。保留所有权利。
Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF alpha) are proinflammatory cytokines that play a critical role in inflammatory bowel disease, as well as in colorectal tumorigenesis. We hypothesize that these cytokines modulate the expression and thus activity of the vitamin D system in colonic epithelial cells. We treated the colon cancer cell line COGA-1A for 6, 12, and 24h with 1,25-dihydroxyvitamin D-3 (1,25-D-3), IL-6, TNFa, and with combinations of these compounds. Using quantitative RT-PCR, we analyzed mRNA expression of genes activating and catabolizing 1,25-D3 (1 alpha-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1)), expression of several vitamin D target genes, as well as expression of cyclooxygenase 2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase. As expected, treatment with 1,25-D3 resulted in an upregulation of CYP24A1, whereas expression of CYP27B1 was not affected. Treatment with TNFa and IL-6 led to decreased expression of the vitamin D activating enzyme CYP27B1. The strong inflammatory property of TNFa was mirrored by its activation of COX-2 and inhibition of prostaglandin E2 (PGE2) catabolism. Interestingly, expression of the calcium ion channel TRPV6 was markedly decreased by TNFa. We conclude from these results that the presence of proinflammatory cytokines might impair activation of 1,25-D3, limiting its anti-inflammatory action. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.