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Caspase-11 is a key upstream modulator for activation of inflammatory response under pathological conditions.In this study,we investigated the roles of caspase-11 in the maturation of interleukin-1β (IL-1β) and development of renal interstitial fibrosis in vivo and in vitro.Mice were subjected to unilateral ureteral obstruction (UUO).The mice were treated with either caspase-11 inhibitor wedelolactone (Wed,30 mg/kg/day,ig) for 7 days or caspase-11 siRNA (10 nmol/20 g body weight per day,iv) for 14 days.The mice were euthanized on day 14,their renal tissue and blood sample were collected.We found that the obstructed kidney had significantly higher caspase-11 levels and obvious tubular injury and interstitial fibrosis.Treatment with Wed or caspase-11 siRNA significantly mitigated renal fibrosis in UUO mice,evidenced by the improved histological changes.Furthermore,caspase-11 inhibition significantly blunted caspase-1 activation,IL-1β maturation,transforming growth factor-β (TGF-β),fibronectin,and collagen I expressions in the obstructed kidney.Renal tubular epithelial NRK-52E cells were treated in vitro with angiotensin (Ang,1 μmol/L),which stimulated caspase-11 activation and IL-1β maturation.Treatment with IL-1β (20 ng/ml) significantly increased the expression of TGF-β,fibronectin,and collagen Ⅰ in the cells.Ang Ⅱ-induced expression of TGF-β,fibronectin,and collagen Ⅰ were suppressed by caspase-11 siRNA or Wed.Finally,we revealed using co-immunoprecipitation that caspase-11 was able to interact with caspase-1 in NRK-52E cells.These results suggest that caspase-11 is involved in UUO-induced renal fibrosis.Elevation of caspase-11 in the obstructed kidney promotes renal fibrosis by stimulating caspase-1 activation and IL-1β maturation.