Inflammatory Bowel Disease Clinic, Department of Gastroenterology, México City, México; Posgrado Ciencias Biológicas, Universidad Nacional Autónoma de México, México City, México.
Clin Exp Immunol. 2014 Jul;177(1):64-75. doi: 10.1111/cei.12285.
Interleukin (IL)-19 and IL-24 belong to the IL-20 subfamily, and are involved in host defence against bacteria and fungi, tissue remodelling and wound healing. Nevertheless, no previous studies have explored their expression in Mexican mestizo patients with inflammatory bowel disease (IBD). The aim of the study was to characterize and to enumerate peripheral and tissue IL-19- and IL-24-producing cells, as well as gene expression in patients with IBD with regard to its clinical activity. We studied a total of 77 patients with ulcerative colitis (UC), 36 Crohn's disease (CD) and 33 patients as control group (without endoscopic evidence of intestinal inflammation). Gene expression was measured by real-time-polymerase chain reaction (RT-PCR). Protein expression was detected in biopsies by immunohistochemistry and in freshly isolated peripheral blood mononuclear cells by flow cytometry. IL-19 and IL-24 gene expression was elevated significantly in patients with active IBD versus the inactive disease and non-inflammatory control groups (P < 0·05). However, IL-19- and IL-24-producing cells were only increased in active CD versus active UC and non-inflammatory tissues (P < 0·05). IL-19 was produced conspicuously by circulating B cells and monocytes in patients with inactive disease (P < 0·05). Conversely, IL-24 was noticeably synthesized by peripheral B cells, CD4(+) T cells, CD8(+) T cells and monocytes in patients with active disease. In conclusion, IL-19- and IL-24-producing cells in active CD patients were increased compared with active UC and non-inflammatory tissues. These cytokines could significantly shape and differentiate inflammatory process, severity and tolerance loss between UC and CD pathophysiology.
白细胞介素 (IL)-19 和 IL-24 属于 IL-20 亚家族,参与宿主对细菌和真菌的防御、组织重塑和伤口愈合。然而,以前没有研究探索过它们在患有炎症性肠病 (IBD) 的墨西哥梅斯蒂索人患者中的表达。本研究的目的是描述和计数外周血和组织中产生 IL-19 和 IL-24 的细胞,并研究 IBD 患者的基因表达与临床活动的关系。我们研究了总共 77 例溃疡性结肠炎 (UC) 患者、36 例克罗恩病 (CD) 患者和 33 例对照组患者(无肠道炎症的内镜证据)。通过实时聚合酶链反应 (RT-PCR) 测量基因表达。通过免疫组织化学在活检组织中以及通过流式细胞术在新鲜分离的外周血单核细胞中检测蛋白表达。与非活动疾病和非炎症性对照组相比,活动期 IBD 患者的 IL-19 和 IL-24 基因表达显著升高 (P < 0·05)。然而,仅在活动期 CD 患者中观察到 IL-19 和 IL-24 产生细胞增加,而在活动期 UC 和非炎症组织中则未观察到 (P < 0·05)。在非活动期疾病患者中,循环 B 细胞和单核细胞显著产生 IL-19 (P < 0·05)。相反,在活动期疾病患者中,外周 B 细胞、CD4+T 细胞、CD8+T 细胞和单核细胞明显合成 IL-24。总之,与活动期 UC 和非炎症组织相比,活动期 CD 患者的 IL-19 和 IL-24 产生细胞增加。这些细胞因子可能显著塑造和分化炎症过程、严重程度和 UC 和 CD 病理生理学之间的耐受丧失。