Role of interleukin-24 in the pathomechanism of inflammatory bowel disease
Ónody Anna Mária
Clinical Medicine
Dr. Reusz György
SE I. Gyermekgyógyászati Klinika tanterme
2023-06-05 14:00:00
Prevention of Chronic Diseases in Childhood
Dr. Szabó Attila
Dr. Vannay Ádám
Dr. Lőrincz Kende Kálmán
Dr. Harangi Ferenc
Dr. Szabó András Lajos
Dr. Schall Eszter
Dr. Szabó Dolóresz Ildikó
In my PhD thesis I investigated the role of interleukin-24 (IL-24) in tissue remodeling during inflammatory bowel disease.
IBD has two main types including Crohn's disease (CD) and ulcerative colitis (UC). IBD is characterized by chronic inflammation, and over time with tissue remodeling of the gastrointestinal tract. The incidence of the disease is increasing worldwide year by year, while causal therapy has not been resolved. More than 70% of CD patients and more than 35% of UC patients need one or more surgical intervention over their lifetime. The aim of our study was to investigate the molecular pathways, mechanisms and markers involved in the pathomechanism of IBD.
Our experiments demonstrated the role of IL-24 in the pathomechanism of tissue remodeling in IBD (25. figure).
25. Figure Schematic model of the proposed mechanism underlying the role of IL-24 in the IBD-associated tissue remodeling. Our results showed increased amount of IL-24 in the inflamed colonic mucosa of IBD patients or DSS treated mice. IBD-related factors, including IL-1ß, LPS or H2O2 are direct inducers of IL-24 in immune cells derived from lamina propria (LPMCs) or peripheral blood (PBMCs). IL-24 enhances the synthesis of pro-fibrotic factors, including TGF-β and PDGF-B in epithelial cells. These growth factors together with IL-24 induce the activation of colonic fibroblast leading to the excessive deposition of extracellular matrix (ECM) components.
We found increased amount of IL-24 in the inflamed colon mucosa of therapy naive children with CD and UC versus control.
In our in vivo experiments, we found that in the absence of the IL-20RB receptor, the symptoms of chemically induced colitis were milder compared to the control group.
The IL-24 enhances the production of TGF-β1 and PDGF-B by epithelial cells both in vivo and in vitro, and it contributes to an increase in the migration capacity of fibroblasts. It also enhances the expression of extracellular matrix components such as MMP-2, -9, TIMP-1, and -2 in fibroblasts in vivo and in vitro as well.
Deeper understanding of the molecular processes of IBD may contribute to the identification of new biomarkers and development of new drugs that may complement the current therapeutic options for the treatment of IBD.
