title: Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model.
abstract: Interleukin-10 functions as a general immunosuppressive cytokine, which also negatively regulates inflammatory responses through complex mechanisms. Recent studies suggested that IL-10 may also inhibit fibrosis in various diseased models. However, the role of IL-10 in renal fibrosis has not been demonstrated. Here, we investigated the effects of IL-10 in the development of renal tubulointerstitial fibrosis by creating the unilateral ureteral obstruction (UUO) model in IL-10 knockout (-/-) mice. We performed sham or unilateral ureteral obstruction surgery in 8-week-old IL-10-/- male mice and age and sex-matched wild type littermates. Mice were killed at 7 days or 14 days post surgery and renal tissues were obtained for RNA, protein, and immunohistochemical analysis. Our results found IL-10 deficiency resulted in enhanced renal fibrosis demonstrated by more severe tubular injury and collagen deposition and higher expression of pro-fibrotic genes (including α-SMA, MMP-2, fibronectin, FSP-1 and vimentin). Our results also found IL-10-/- UUO mice developed more severe renal inflammation with a significant increase in inflammatory cells infiltration, and upregulation of inflammatory chemokines (MCP-1 and RANTES), and cytokines (TNF-α, IL-6, IL-8, and M-CSF). Further study revealed that enhanced renal inflammation and fibrosis was associated with significantly increased activation of both TGF-β/Smad3 and NF-κB signaling pathways. In summary, our study provides the direct evidence that IL-10 is an endogenous cytokine that has a key role in protecting against development of renal inflammation and fibrosis. Enhancement of IL-10 expression could be a potential anti-fibrosis therapy for patients with chronic kidney diseases.
authors: Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors: Yuanmeng
authors: Y
authors: Jin
authors: Ruijie
authors: R
authors: Liu
authors: Jingyuan
authors: J
authors: Xie
authors: Huabao
authors: H
authors: Xiong
authors: John Cijiang
authors: JC
authors: He
authors: Nan
authors: N
authors: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D016753:Interleukin-10 / Q000172:deficiency*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009393:Nephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009400:Nephrosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism* / Q000473:pathology
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10