Characterization of IL-19, -20, and -24 in acute and chronic kidney diseases reveals a pro-fibrotic role of IL-24

• Published in: Journal of translational medicine 2020-04, Vol.18 (1), p.172-172, Article 172
• Main Authors: Pap, Domonkos, Veres-Székely, Apor, Szebeni, Beáta, Rokonay, Réka, Ónody, Anna, Lippai, Rita, Takács, István Márton, Tislér, András, Kardos, Magdolna, Oswald, Franz, Fekete, Andrea, Szabó, Attila J, Vannay, Ádám
• Format: Article
• Language: English
• Subjects: Acute kidney disease; Analysis; Animal models; Animals; Apoptosis; Biopsy; Blood platelets; Cell culture; Cell growth; Chronic kidney disease; Chronic kidney failure; Clear cell-type renal cell carcinoma; Connective tissue growth factor; Cytokines; Diabetes; Diabetes mellitus; Diabetic nephropathies; Diabetic nephropathy; Disease Models, Animal; Epithelial cells; Experiments; Extracellular matrix; Fibroblasts; Fibronectin; Fibronectins; Fibrosis; Growth factors; Humans; Hydrogen Peroxide; Immunoglobulin A; Interleukin 1; Interleukin 19; Interleukin 20; Interleukin 20 subfamily; Interleukin 24; Interleukins; Ischemia; Kidney - pathology; Kidney diseases; Kidney Diseases - pathology; Kidney fibrosis; Laboratory animals; Leukocytes, Mononuclear; Lipopolysaccharides; Localization; Lupus; Lupus nephritis; Medical research; Mice; Mitogens; Nephritis; Nephropathy; Penicillin; Peripheral blood mononuclear cells; Proteins; Renal Insufficiency, Chronic - pathology; Reperfusion; Rodents; Streptozocin; Transforming growth factor-b1; Ureteral Obstruction - pathology
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02338-4

Recently, the role of IL-19, IL-20 and IL-24 has been reported in renal disorders. However, still little is known about their biological role. Localization of IL-20RB was determined in human biopsies and in the kidneys of mice that underwent unilateral ureteral obstruction (UUO). Renal Il19, Il20 and Il24 expression was determined in ischemia/reperfusion, lipopolysaccharide, streptozotocin, or UUO induced animal models of kidney diseases. The effects of H O , LPS, TGF-β1, PDGF-B and IL-1β on IL19, IL20 and IL24 expression was determined in peripheral blood mononuclear cells (PBMCs). The extents of extracellular matrix (ECM) and α-SMA, Tgfb1, Pdgfb, and Ctgf expression were determined in the kidneys of Il20rb knockout (KO) and wild type (WT) mice following UUO. The effect of IL-24 was also examined on HK-2 tubular epithelial cells and NRK49F renal fibroblasts. IL-20RB was present in the renal biopsies of patients with lupus nephritis, IgA and diabetic nephropathy. Amount of IL-20RB increased in the kidneys of mice underwent UUO. The expression of Il19, Il20 and Il24 increased in the animal models of various kidney diseases. IL-1β, H O and LPS induced the IL19, IL20 and IL24 expression of PBMCs. The extent of ECM, α-SMA, fibronectin, Tgfb1, Pdgfb, and Ctgf expression was lower in the kidney of Il20rb KO compared to WT mice following UUO. IL-24 treatment induced the apoptosis and TGF-β1, PDGF-B, CTGF expression of HK-2 cells. Our data confirmed the significance of IL-19, IL-20 and IL-24 in the pathomechanism of renal diseases. Furthermore, we were the first to demonstrate the pro-fibrotic effect of IL-24.