| First Author | Jin Y | Year | 2013 |
| Journal | Lab Invest | Volume | 93 |
| Issue | 7 | Pages | 801-11 |
| PubMed ID | 23628901 | Mgi Jnum | J:198752 |
| Mgi Id | MGI:5499077 | Doi | 10.1038/labinvest.2013.64 |
| Citation | Jin Y, et al. (2013) Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model. Lab Invest 93(7):801-11 |
| abstractText | 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 alpha-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-alpha, 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-beta/Smad3 and NF-kappaB 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. |
