Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis
Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis
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DOI：
10.1007/s00535-010-0245-1
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发表时间：
2010-10-01
影响因子：
6.3
通讯作者：
Andoh, Akira
中科院分区：
文献类型：
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作者：
Kobori, Ayako;Yagi, Yuhki;Andoh, Akira
白细胞介素(IL)-33是属于IL-1家族的细胞因子。IL-33已被证明在免疫细胞中引起th2样细胞因子反应。在这项研究中，我们研究了IL-33在炎症性肠病（IBD）患者炎症粘膜中的表达，并表征了IL-33在人结肠上皮下肌成纤维细胞（semf）中表达的分子机制。实时聚合酶链反应（real-time polymerase chain reaction， PCR）检测IL-33 mRNA表达。免疫组化法检测IL-33在IBD黏膜中的表达。IL-33 mRNA表达在溃疡性结肠炎（UC）患者的活动性病变中显著升高，但在UC患者的非活动性病变或活动性或非活动性克罗恩病患者的病变中未检测到。结肠semf被确定为粘膜中IL-33的主要来源。IL-1 β和肿瘤坏死因子- α (tnf - α)显著提高离体结肠semf中IL-33 mRNA和蛋白的表达。IL-1 β和tnf - α不影响肠上皮细胞系（HT-29和Caco-2细胞）IL-33的表达。这种IL-1 β和tnf α诱导的IL-33 mRNA表达是通过p42/44丝裂原活化蛋白激酶（MAPK）途径依赖的核因子(NF)- κ B和激活蛋白(AP)-1的激活介导的。来自结肠semf的IL-33可能在UC的病理生理中起重要作用。
Interleukin (IL)-33 is a cytokine belonging to the IL-1 family. IL-33 has been shown to elicit a Th2-like cytokine response in immune cells. In this study, we investigated IL-33 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-33 expression in human colonic subepithelial myofibroblasts (SEMFs).IL-33 mRNA expression was determined by real-time polymerase chain reaction (PCR). IL-33 expression in the IBD mucosa was evaluated by immunohistochemical methods.IL-33 mRNA expression was significantly elevated in active lesions from patients with ulcerative colitis (UC), but was not detected in inactive lesions from UC patients or in lesions from patients with either active or inactive Crohn's disease. Colonic SEMFs were identified as a major source of IL-33 in the mucosa. IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) significantly enhanced IL-33 mRNA and protein expression in isolated colonic SEMFs. IL-1 beta and TNF-alpha did not affect IL-33 expression in intestinal epithelial cell lines (HT-29 and Caco-2 cells). This IL-1 beta- and TNF-alpha-induced IL-33 mRNA expression was mediated by p42/44 mitogen activated protein kinase (MAPK) pathway-dependent activation of nuclear factor (NF)-kappa B and activator protein (AP)-1.IL-33, derived from colonic SEMFs, may play an important role in the pathophysiology of UC.