Expression of IL-24, an Activator of the JAK1/STAT3/SOCS3 Cascade, Is Enhanced in Inflammatory Bowel Disease
Expression of IL-24, an Activator of the JAK1/STAT3/SOCS3 Cascade, Is Enhanced in Inflammatory Bowel Disease
复制标题
DOI：
10.4049/jimmunol.0804169
复制
发表时间：
2009-07-01
影响因子：
4.4
通讯作者：
Fujiyama, Yoshihide
中科院分区：
文献类型：
--
作者：
Andoh, Akira;Shioya, Makoto;Fujiyama, Yoshihide
IL-24是细胞因子IL-10家族的成员。在这项研究中，我们研究了IL-24在炎症性肠病（IBD）患者的炎症粘膜中的表达，并表征了IL-24在人结肠上皮下肌成纤维细胞（SEMF）中表达的分子机制。免疫组化法检测IL-24在IBD黏膜中的表达。采用实时荧光定量PCR和ELISA法分别检测IL-24 mRNA和蛋白表达。通过EMSA分析和报告基因测定分别评估AP-1和C/EBP DNA结合活性和IL-24启动子活性。IL-24 mRNA表达在溃疡性结肠炎和克罗恩病患者的活动性病变中显著升高。结肠SEMF被鉴定为粘膜中IL-24的主要来源。在分离的结肠SEMF中，IL-1 β而非IL-17 A、TNF-α或IFN-γ显著增强IL-24 mRNA和蛋白表达。IL-1 β诱导的IL-24 mRNA表达是通过激活转录因子AP-1和C/EBP-β介导的。IL-1 β、IL-24诱导HT-29结肠上皮细胞JAK 1/STAT-3磷酸化和SOCS 3表达的作用也涉及IL-24 mRNA稳定化的诱导。IL-24不调节HT-29细胞的增殖，但显著增加膜结合粘蛋白（MUC 1、MUC 3和MUC 4）的mRNA表达。来源于结肠SEMF的IL-24作用于结肠上皮细胞以引发JAK 1/STAT-3活化以及SOCS 3和粘蛋白的表达，支持它们对IBD中的粘膜炎症的抑制作用。免疫学杂志，2009，183：687-695.
IL-24 is a member of the IL-10 family of cytokines. In this study, we investigated IL-24 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-24 expression in human colonic subepithelial myofibroblasts (SEMFs). IL-24 expression in the IBD mucosa was evaluated by immunohistochemical methods. IL-24 mRNA and protein expression was determined by real-time PCR and ELISA, respectively. AP-1 and C/EBP DNA-binding activity and IL-24 promoter activity were assessed by EMSA analysis and a reporter gene assay, respectively. IL-24 mRNA expression was significantly elevated in active lesions from patients who have ulcerative colitis and Crohn's disease. Colonic SEMFs were identified as a major source of IL-24 in the mucosa. IL-1 beta, but not IL-17A, TNF-alpha, or IFN-gamma, significantly enhanced IL-24 mRNA and protein expression in isolated colonic SEMFs. The IL-1 beta-induced IL-24 mRNA expression was mediated by the activation of the transcription factors, AP-1 and C/EBP-beta. Induction of IL-24 mRNA stabilization was also involved in the effects of IL-1 beta, IL-24 induced JAK1/STAT-3 phosphorylation and SOCS3 expression in HT-29 colonic epithelial cells. IL-24 did not modulate the proliferation of HT-29 cells, but significantly increased the mRNA expression of membrane-bound mucins (MUC1, MUC3, and MUC4). IL-24 derived from colonic SEMFs acts on colonic epithelial cells to elicit JAK1/STAT-3 activation and the expression of SOCS3 and mucins, supporting their suppressive effects on mucosal inflammation in IBD. The Journal of Immunology, 2009, 183: 687-695.