Abstract
BackgroundRecently, 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.MethodsPresence 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.Results 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 H2O2 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.ConclusionOur study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.
Highlights
Increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD)
Protein level of IL-24 was increased in inflamed mucosa of pediatric patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to controls, but it was unchanged in the non-inflamed colonic region of patients with CD (Fig. 1a, c)
Presence of IL‐24 in mice with dextran sodium sulfate (DSS)‐induced colitis To further study the role of IL-24 in intestinal pathophysiology, we investigated its expression in the colon of mice with DSS induced colitis
Summary
Increased interleukin (IL)-24 expression has been demonstrated in the colon biopsies of adult patients with inflammatory bowel disease (IBD). Incidence of inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) has almost doubled during the last two decades, indicating its growing significance [1, 2]. As a consequence of chronic intestinal inflammation multitude of cytokines and growth factors are released contributing to intense mucosal remodeling. In this process, subepithelial myofibroblasts (MFs) play a determinative role. Chronic inflammation in IBD may lead to permanent activation of MFs shifting the processes of tissue repair toward the excessive deposition of extracellular matrix (ECM).
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