1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
ELKH-SE Pediatrics and Nephrology Research Group, 53-54 Bókay J. Street, Budapest, H-1083, Hungary.
J Transl Med. 2021 Jun 2;19(1):237. doi: 10.1186/s12967-021-02890-7.
Recently, increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD). However, the role of IL-24 in the pathomechanism of IBD is still largely unknown.
Presence of IL-24 was determined in the samples of children with IBD and in the colon of dextran sodium sulfate (DSS) treated mice. Effect of inflammatory factors on IL24 expression was determined in peripheral blood (PBMCs) and lamina propria mononuclear cells (LPMCs). Also, the impact of IL-24 was investigated on HT-29 epithelial cells and CCD-18Co colon fibroblasts. Expression of tissue remodeling related genes was investigated in the colon of wild type (WT) mice locally treated with IL-24 and in the colon of DSS treated WT and Il20rb knock out (KO) mice.
Increased amount of IL-24 was demonstrated in the serum and colon samples of children with IBD and DSS treated mice compared to that of controls. IL-1β, LPS or HO treatment increased the expression of IL24 in PBMCs and LPMCs. IL-24 treatment resulted in increased amount of TGF-β and PDGF-B in HT-29 cells and enhanced the expression of extracellular matrix (ECM)-related genes and the motility of CCD-18Co cells. Similarly, local IL-24 treatment increased the colonic Tgfb1 and Pdgfb expression of WT mice. Moreover, expression of pro-fibrotic Tgfb1 and Pdgfb were lower in the colon of DSS treated Il20rb KO compared to that of WT mice. The disease activity index of colitis was less severe in DSS treated Il20rb KO compared to WT mice.
Our study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.
最近，在成人炎症性肠病（IBD）患者的结肠活检中发现白细胞介素（IL）-24 的表达增加。然而，IL-24 在 IBD 发病机制中的作用仍知之甚少。
在患有 IBD 的儿童的样本和用葡聚糖硫酸钠（DSS）处理的小鼠的结肠中确定 IL-24 的存在。在外周血（PBMCs）和粘膜固有层单核细胞（LPMCs）中确定炎症因子对 IL24 表达的影响。此外，还研究了 IL-24 对 HT-29 上皮细胞和 CCD-18Co 结肠成纤维细胞的影响。在局部用 IL-24 处理的野生型（WT）小鼠的结肠和用 DSS 处理的 WT 和 Il20rb 敲除（KO）小鼠的结肠中研究组织重塑相关基因的表达。
与对照组相比，患有 IBD 的儿童和 DSS 处理的小鼠的血清和结肠样本中 IL-24 的含量增加。IL-1β、LPS 或 HO 处理增加了 PBMCs 和 LPMCs 中 IL24 的表达。IL-24 处理导致 HT-29 细胞中 TGF-β和 PDGF-B 的含量增加，并增强了 CCD-18Co 细胞的细胞外基质（ECM）相关基因的表达和运动性。同样，局部 IL-24 处理增加了 WT 小鼠结肠中的 Tgfb1 和 Pdgfb 表达。此外，与 WT 小鼠相比，DSS 处理的 Il20rb KO 小鼠结肠中促纤维化基因 Tgfb1 和 Pdgfb 的表达较低。与 WT 小鼠相比，DSS 处理的 Il20rb KO 小鼠的结肠炎疾病活动指数较轻。
我们的研究表明，IL-24 可能通过促进促纤维化过程在 IBD 患者的粘膜重塑中发挥重要作用。
