Regulated production of the chemokine CCL28 in human colon epithelium
Regulated production of the chemokine CCL28 in human colon epithelium
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DOI：
10.1152/ajpgi.00162.2004
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发表时间：
2004-11-01
影响因子：
4.5
通讯作者：
Kagnoff, MF
中科院分区：
文献类型：
--
作者：
Ogawa, H;Iimura, M;Kagnoff, MF
趋化因子CCL 28由上皮细胞在几个粘膜部位组成性表达，并被认为起T细胞和伊加B细胞亚群的稳态化学引诱物的作用，并介导抗微生物活性。我们在此报告的调节CCL 28在人类结肠上皮细胞的促炎细胞因子IL-1，细菌鞭毛蛋白，正丁酸，微生物代谢的产物。在体内，与正常人结肠相比，病理性炎症的上皮中CCL 28显著增加。人结肠和小肠异种移植物用于体内模拟人肠上皮。异种移植物组成型表达很少，如果有的话，CCL 28 mRNA或蛋白质。在用促炎细胞因子IL-1刺激后，CCL 28 mRNA和蛋白在结肠上皮中显著增加，但在小肠异种移植物中没有，尽管两者都上调了另一种原型趋化因子CXCL 8的表达，以响应相同的刺激。在使用人结肠上皮细胞系的CCL 28调节的研究中，促炎刺激，包括IL-1、细菌鞭毛蛋白和细菌感染，显著上调CCL 28 mRNA表达和蛋白质产生。此外，CCL 28的mRNA表达和蛋白分泌的这些细胞显着增加的短链脂肪酸正丁酸酯，和IL-1或鞭毛蛋白刺激的上调CCL 28的结肠上皮细胞协同增加的预处理细胞与正丁酸酯。与其上调表达的促炎刺激，CCL 28 mRNA表达减弱的NF-κ B激活的药理学抑制剂。这些发现表明，CCL 28在人类结肠上皮中作为“炎性”趋化因子发挥作用，并提示CCL 28可能起反调节结肠炎症的作用。
The chemokine CCL28 is constitutively expressed by epithelial cells at several mucosal sites and is thought to function as a homeostatic chemoattractant of subpopulations of T cells and IgA B cells and to mediate antimicrobial activity. We report herein on the regulation of CCL28 in human colon epithelium by the proinflammatory cytokine IL-1, bacterial flagellin, and n-butyrate, a product of microbial metabolism. In vivo, CCL28 was markedly increased in the epithelium of pathologically inflamed compared with normal human colon. Human colon and small intestinal xenografts were used to model human intestinal epithelium in vivo. Xenografts constitutively expressed little, if any, CCL28 mRNA or protein. After stimulation with the proinflammatory cytokine IL-1, CCL28 mRNA and protein were significantly increased in the epithelium of colon but not small intestinal xenografts, although both upregulated the expression of another prototypic chemokine, CXCL8, in response to the identical stimulus. In studies of CCL28 regulation using human colon epithelial cell lines, proinflammatory stimuli, including IL-1, bacterial flagellin, and bacterial infection, significantly upregulated CCL28 mRNA expression and protein production. In addition, CCL28 mRNA expression and protein secretion by those cells were significantly increased by the short-chain fatty acid n-butyrate, and IL-1- or flagellin-stimulated upregulation of CCL28 by colon epithelial cells was synergistically increased by pretreatment of cells with n-butyrate. Consistent with its upregulated expression by proinflammatory stimuli, CCL28 mRNA expression was attenuated by pharmacological inhibitors of NF-kappaB activation. These findings indicate that CCL28 functions as an "inflammatory" chemokine in human colon epithelium and suggest the notion that CCL28 may act to counterregulate colonic inflammation.