Interleukin-24 regulates mucosal remodeling in inflammatory bowel diseases

Abstract

Background 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. Methods 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. 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. Conclusion Our study suggest that IL-24 may play a significant role in the mucosal remodeling of patients with IBD by promoting pro-fibrotic processes.

Identification of Pharmacological Autophagy Regulators of Active Ulcerative Colitis

“…In this study, the genes (IL24, NAMPT, and CASP4) in the turquoise module were not further analyzed. Compared with the control group, IL24 expression was increased in serum and colon samples from pediatric IBD patients and dextran sulfate sodium (DSS) induced colitis mouse models ( Onody et al, 2021 ). Besides, NAMPT was intensively upregulated in inflammation, including IBD ( Gerner et al, 2018 ).…”

IL-37 protects against airway remodeling by reversing bronchial epithelial–mesenchymal transition via IL-24 signaling pathway in chronic asthma

“…Another study showed that IL-24 −/− mice were protected against bleomycin-induced lung fibrosis by reducing TGF-β1 production and M2 macrophage infiltration [ 24 ]. A recent study reported that IL-24 treatment significantly increased the levels of TGF‑β and PDGF‑B in HT‑29 epithelial cells and upregulated the levels of ECM-associated genes in CCD‑18Co colon fibroblasts, indicating that IL-24 might contribute to the development of mucosal remodeling in IBD patients [ 19 ]. Contrary to the above results, Corbin et al revealed that IL-24 inhibited EMT-related transcription factors and TGF-β in lung cancer cell lines and lung cancer models [ 43 ].…”

“…As a pleiotropic cytokine, its activity mainly depends on heterodimeric receptor (IL-20RA/IL-20RB and IL-22RA/IL-20RB) expression patterns in target tissues to mediate downstream signaling pathways [ 14 ]. Recently, a series of studies have reported the connection between IL-24 and immune inflammatory diseases, including asthma [ 15 ], psoriasis [ 16 ], systemic lupus erythematosus [ 17 ], atopic dermatitis [ 18 ], inflammatory bowel disease [ 19 , 20 ], and rheumatoid arthritis [ 21 ]. Despite its extensive antitumor effect [ 22 ], several lines of evidence have revealed that IL-24 also shows a profibrotic effect on tissue remodeling.…”

Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases

“…Onody et al also observed increased expression of IL-24 in the serum and colon samples of children with IBD. IL-24 treatment stimulated HT-29 cells to produce TGF-β and PDGF-B, and CCD-18Co cells to express extracellular matrix (ECM)-related genes, suggesting the potential role of IL-24 in the remodeling of colon tissue [ 58 ]. In a follow-up in vivo study, they found that IL-20 receptor cytokine signaling is pathogenic in the dextran sulfate sodium (DSS)-induced colitis model, as Il20rb deficiency ameliorates disease development [ 58 ].…”

“…IL-24 treatment stimulated HT-29 cells to produce TGF-β and PDGF-B, and CCD-18Co cells to express extracellular matrix (ECM)-related genes, suggesting the potential role of IL-24 in the remodeling of colon tissue [ 58 ]. In a follow-up in vivo study, they found that IL-20 receptor cytokine signaling is pathogenic in the dextran sulfate sodium (DSS)-induced colitis model, as Il20rb deficiency ameliorates disease development [ 58 ]. However, it was noted that IL20rb deficiency leads to the loss of not only IL-24-, but also IL-19- and IL-20-mediated signaling; therefore, a more specific study is required to confirm the role of IL-24 in this animal model.…”