Abstract
BackgroundRecently, 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.MethodsLocalization 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 H2O2, 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.ResultsIL-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, H2O2 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.ConclusionsOur 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.
Highlights
The role of IL-19, IL-20 and interleukin 24 (IL-24) has been reported in renal disorders
Taken together our results demonstrate that Peripheral blood mononuclear cell (PBMC) are capable to produce the cytokines of the IL-20 subfamily in response to the prominent mediators of renal diseases, there is a clear difference between the PBMCs of healthy adults and those of patients with chronic kidney disease (CKD), which may be due to the previous activation of the PBMCs originating from patients with CKD [29]
In line with our in vivo experiments demonstrating that the lack of IL-20RB is associated with decreased synthesis of Tgfb1, Pdgfb and Ctgf, we found that IL-24 treatment induces Transforming growth factor beta-1 (TGF-β1), plateletderived growth factor B (PDGF-B) and connective tissue growth factor (CTGF) synthesis of Human proximal tubular epithelial cells (HK-2) tubular epithelial cells in vitro (Fig. 6d–l)
Summary
The role of IL-19, IL-20 and IL-24 has been reported in renal disorders. still little is known about their biological role. The prevalence of chronic kidney disease (CKD) is estimated to be 8–16% worldwide, and is rapidly increasing [1]. The IL-20 subfamily of cytokines are mainly produced by immune cells and have been suggested to enhance tissue repair processes [5]. Our previous genome-wide analysis performed on new-born rat kidneys suggested the possible role of IL-24 in the renal tissue remodeling, as well [9]. All these data indicate a role of the IL-20 subfamily in CKD, little is known about the underlying mechanisms. The role of investigated cytokines in CKD were examined using Il20rb KO mice and HK-2 tubular epithelial cells
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