The role of interleukin-24 in the pathomechanism of IBD-associated tissue remodeling

Veres-Székely, Apor and Ónody, Anna and Sziksz, Erna and Rokonay, Réka and Pap, Domonkos and Lippai, Rita and Takács, István M. and Veres, Gábor and Cseh, Áron and Szabó, Attila J. and Vannay, Ádám (2018) The role of interleukin-24 in the pathomechanism of IBD-associated tissue remodeling. In: Falk konferencia, Svájc.

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Abstract

Abstract: Introduction: Intestinal fibrosis is a serious complication of inflammatory bowel diseases (IBD). Interleukin(IL)-24 is a member of IL-20 cytokine subfamily, which regulatory effect is suspected in connection with inflammation, apoptosis or tissue remodeling in other organs. Increased level of IL-24 was described in the colon of patients with active IBD, however its biological role is still poorly understood. Methods: Colonic presence of IL-24 and its receptor IL-20RB was investigated in the dextran-sodium sulfate (DSS) induced mice model of IBD (n=8; C57BL/6J). Impact of IL-24 on colonic extracellular matrix (ECM) production was investigated in the DSS treated wild type and IL-20RB knockout (KO) mice. Effect of intracolonic injection of IL-24 was also investigated. The role of IL-24 treatment on the expression of fibrosis related genes was investigated in colonic epithelial (HT-29) and fibroblast (CCD-18Co) cells. Results: Expression of IL-24 increased in colonic tissue of DSS-treated mice compared to controls. Lack of IL-24 receptor resulted in reduced ECM deposition in IL-20RB KO mice compared to wild type group. Local administration of IL-24 increased the expression of the fibrosis associated genes in the colon. IL-24 treatment increased the expression of TGF-ß1 and PDGF-B in HT-29, and that of COL1, COL3, FN1, MMP2, -9, TIMP1, -2 in CCD-18Co cells. Discussion: IL-24 may promote tissue remodeling shifted toward an excessive deposition of ECM components directly by acting on fibroblast and indirectly via induction of pro-fibrotic factors on epithelial cells. Our data suggest that inhibition of IL-24 may have a significant anti-fibrotic effect. Support: OTKA-K116928, VKE-2017-00006,EFOP-3.6.3-VEKOP-16-2017-00009,MTA-SE Pediatrics and Nephrology Research Group, János Bolyai Research Scholarship of the Hungarian Academy of Sciences

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