BACKGROUND Recently, involvement of IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, their impact on the pathomechanism of coeliac disease (CD) is still completely unknown. METHODS Expression of IL19, IL20 and IL24 was measured by real-time RT-PCR, protein amount of IL-24, α smooth muscle actin (α-SMA) and fibronectin (FN) was determined by Western-blot analysis in the duodenal biopsies of therapy naive children with CD and controls. Localization of IL-24 and IL-20RB was investigated by immunofluorescent staining in the duodenal mucosa. Effect of recombinant IL-1β, TNF-α, TGF-β and IL-17 treatment on the expression of IL19, IL20, IL24 and their receptors was investigated by real-time RT-PCR in small intestinal epithelial cells (FHs74Int), in primary duodenal myofibroblasts (pdMFs) and in peripheral blood mononuclear cells (PBMCs). Effect of IL-24 on H2O2 treated FHs74Int cells and on pdMFs was measured by MTT, LDH, Annexin V assays, real-time RT-PCR and by fluorescent microscopy. RESULTS We found increased level of IL-24 (3.3×, p < 0.05), α-SMA (2.4×, p < 0.05) and FN (2.3×, p < 0.05) in the duodenal mucosa and increased expression of IL19 (3.6×, p < 0.05) and IL24 (5.2×, p < 0.05) in the PBMCs of children with CD compared to that of controls. IL-1β was a strong inducer of IL24 expression of FHs74Int cells (9.9×, p < 0.05), pdMFs (552.9×, p < 0.05) or PBMCs (17.2×, p < 0.05), as well. IL-24 treatment reduced the number of apoptotic cells (0.5×, p < 0.05) and decreased the expression of inflammatory factors, including IL1A, IL6 and TNF of H2O2-treated FHs74Int cells. IL-24 decreased the proliferation (0.6×, p < 0.05) of PDGF-B treated pdMFs. Moreover, IL-24 treatment altered the morphology of pdMFs by influencing the size of the angles between stress fibers and the longitudinal axis of the cells (2.0×, p < 0.05) and the expression of cytoskeletal components, including ACTA2, ACTB, VIM, SNAI1 and SNAI2. CONCLUSION Our results suggest that IL-24 plays a significant role in the maintenance of duodenal mucosal integrity in CD.

中文翻译：

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IL-24在乳糜泻儿童黏膜重塑中的作用。

背景技术近来，已经报道了IL-19，IL-20和IL-24参与与组织重塑有关的炎性疾病。但是，它们对乳糜泻（CD）发病机理的影响仍然是完全未知的。方法采用实时RT-PCR法检测IL19，IL20和IL24的表达，并通过Western-blot法检测十二指肠活检组织中IL-24，α平滑肌肌动蛋白（α-SMA）和纤连蛋白（FN）的蛋白含量。天真的儿童CD和对照的治疗方法。通过免疫荧光染色在十二指肠粘膜中研究了IL-24和IL-20RB的定位。通过实时RT-PCR研究重组IL-1β，TNF-α，TGF-β和IL-17对小肠上皮细胞（FHs74Int）中IL19，IL20，IL24及其受体表达的影响，在原发性十二指肠肌成纤维细胞（pdMFs）和外周血单核细胞（PBMCs）中。IL-24对H2O2处理的FHs74Int细胞和pdMFs的作用通过MTT，LDH，膜联蛋白V测定，实时RT-PCR和荧​​光显微镜进行了测量。结果我们发现十二指肠粘膜中IL-24（3.3x，p <0.05），α-SMA（2.4x，p <0.05）和FN（2.3x，p <0.05）水平升高，IL19（3.6）升高。与对照组相比，患有CD的儿童的PBMC中的×，p <0.05）和IL24（5.2x，p <0.05）。IL-1β也是FHs74Int细胞（9.9x，p <0.05），pdMFs（552.9x，p <0.05）或PBMC（17.2x，p <0.05）IL24表达的强诱导剂。IL-24治疗可减少凋亡细胞数量（0.5x，p <0.05），并减少包括IL1A在内的炎症因子的表达，H2O2处理的FHs74Int细胞的IL6和TNF。IL-24降低了PDGF-B处理的pdMF的增殖（0.6x，p <0.05）。此外，IL-24处理通过影响应力纤维与细胞纵轴之间的夹角大小（2.0x，p <0.05）和细胞骨架成分（包括ACTA2，ACTB，VIM， SNAI1和SNAI2。结论我们的结果表明IL-24在CD的十二指肠粘膜完整性的维持中起着重要作用。SNAI1和SNAI2。结论我们的结果表明IL-24在CD的十二指肠粘膜完整性的维持中起着重要作用。SNAI1和SNAI2。结论我们的结果表明IL-24在CD的十二指肠粘膜完整性的维持中起着重要作用。