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

Abstract

Background: 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. Methods: 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 2 O 2 , 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. Results: 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 2 O 2 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. Conclusions: 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.

Interleukin-24 regulates mucosal remodeling in inflammatory bowel diseases

“…7 ). These results are in accordance with our previous study demonstrating decreased ECM deposition in the kidney of Il20rb KO mice underwent unilateral ureteral obstruction compared to that of WT animals [ 18 ]. Taken together our above in vivo experiment demonstrate that IL-20 cytokines have strong and multiple effects on tissue remodeling of the inflamed colon.…”

“…1 ). Indeed, similarly to recent studies [ 19 ] we found that IL-1ß acts as an inducer of IL-24 synthesis, however our data, in line with our previous results [ 18 ] demonstrated that LPS or H 2 O 2 treatment has similar or even stronger effect on IL-24 synthesis in PBMCs and LPMCs. These data fit well into the literature suggesting the regulatory effect of LPS and IL-1ß on the IL-24 synthesis of immune cells [ 34 ].…”

“…Surprisingly, in our experiments IL-24 treatment did not affect the viability of HT-29 colon epithelial cells (Additional file 2 ). More interestingly, similarly to our previous study on HK-2 renal tubular epithelial cells [ 18 ], we found that IL-24 induces HT-29 colon epithelial cells to synthesize TGF-β1 and PDGF-B (Fig. 3 ).…”

“…These cytokines are mainly produced by leukocytes [ 9 , 10 ] and also by other cell types including epithelial cells and MFs [ 11 , 12 ]. The most well-known function of the subfamily is the regulation of innate immune responses [ 13 – 15 ], however recently, we and others suggested its importance in the process of tissue repair and fibrosis of different organs [ 16 – 18 ]. Previously, increased presence of IL-24 was demonstrated in the intestinal biopsies of patients with IBD and coeliac disease [ 19 – 21 ].…”

IL-19 Promotes Nasal Mucosal Tissue Remodeling in Chronic Rhinosinusitis Patients By Upregulating Fibronectin and Collagen Ι Expressions in Fibroblasts Via NF-κB-Smad2/3 Signaling Pathways

“…It can also increase the expression of TGF, TNF, and Col1 and promotes the proliferation and migration of activated HSCs [21]. In psoriasis, IL-20 stimulates monocytes to produce pro-in ammatory cytokines and indirectly exerts its effect on keratinocyte proliferation through immune cells in the skin [22].In renal brosis disease, the pro-brotic effects of IL-19, IL-22, and IL-24 on the kidney was con rmed in a mouse renal disease model [23]. As a crucial member of the IL-20 subfamily, IL-19 has been found to be highly expressed in many chronic in ammatory diseases, such as psoriasis and asthma.…”