Enalapril inhibits tubulointerstitial inflammation and NLRP3 inflammasome expression in BSA-overload nephropathy of rats
Abstract
Li-hong DING, Dan LIU, Min XU, Hong LIU, Min WU, Ri-ning TANG, Lin-li LV, Kun-ling MA, Bi-cheng LIU*
Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China
Aim: Proteinuria is not only a common marker of renal disease, but also involved in renal tubulointerstitial inflammation and fibrosis. The aim of this study was to investigate the mechanisms underlying the protective effects of enalapril, an ACEI, against nephropathy in rats.
Methods: Wistar rats underwent unilateral right nephrectomy, and then were treated with BSA (5 g·kg-1·d-1, ip), or BSA plus enalapril (0.5 g·kg-1·d-1, po) for 9 weeks. The renal lesions were evaluated using histology and immunohistochemistry. The expression of NLRP3, caspase-1, IL-1β, and IL-18 was analyzed using immunohistochemistry, RT-PCR and Western blot.
Results: BSA-overload resulted in severe proteinuria, which peaked at week 7, and interstitial inflammation with prominent infiltration of CD68+ cells (macrophages) and CD3+ cells (T lymphocytes), particularly of CD20+ cells (B lymphocytes). BSA-overload markedly increased the expression of NLRP3, caspase-1, IL-1β, and IL-18 in the proximal tubular epithelial cells, and in inflammatory cells as well. Furthermore, the expression of IL-1β or IL-18 was significantly correlated with proteinuria (IL-1β: r=0.757; IL-18: r=0.834). These abnormalities in BSA-overload rats were significantly attenuated by concurrent administration of enalapril.
Conclusion: Enalapril exerts protective effects against BSA-overload nephropathy in rats via suppressing NLRP3 inflammasome expression and tubulointerstitial inflammation.
Keywords: proteinuria; tubulointerstitial inflammation; NLRP3 inflammasome; enalapril
This study was supported by grants from the Key Project of the National Natural Science Foundation (No 81130010), National Key Basic Research Project (“973”) (No 2012CB517700), and Natural Science Foundation of Jiangsu Province (No BK201106; all to Bi-cheng LIU, Principle Investigator).
* To whom correspondence should be addressed.
E-mail liubc64@163.com
Received 2014-02-12 Accepted 2014-05-26
Keywords:
Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China
Aim: Proteinuria is not only a common marker of renal disease, but also involved in renal tubulointerstitial inflammation and fibrosis. The aim of this study was to investigate the mechanisms underlying the protective effects of enalapril, an ACEI, against nephropathy in rats.
Methods: Wistar rats underwent unilateral right nephrectomy, and then were treated with BSA (5 g·kg-1·d-1, ip), or BSA plus enalapril (0.5 g·kg-1·d-1, po) for 9 weeks. The renal lesions were evaluated using histology and immunohistochemistry. The expression of NLRP3, caspase-1, IL-1β, and IL-18 was analyzed using immunohistochemistry, RT-PCR and Western blot.
Results: BSA-overload resulted in severe proteinuria, which peaked at week 7, and interstitial inflammation with prominent infiltration of CD68+ cells (macrophages) and CD3+ cells (T lymphocytes), particularly of CD20+ cells (B lymphocytes). BSA-overload markedly increased the expression of NLRP3, caspase-1, IL-1β, and IL-18 in the proximal tubular epithelial cells, and in inflammatory cells as well. Furthermore, the expression of IL-1β or IL-18 was significantly correlated with proteinuria (IL-1β: r=0.757; IL-18: r=0.834). These abnormalities in BSA-overload rats were significantly attenuated by concurrent administration of enalapril.
Conclusion: Enalapril exerts protective effects against BSA-overload nephropathy in rats via suppressing NLRP3 inflammasome expression and tubulointerstitial inflammation.
Keywords: proteinuria; tubulointerstitial inflammation; NLRP3 inflammasome; enalapril
This study was supported by grants from the Key Project of the National Natural Science Foundation (No 81130010), National Key Basic Research Project (“973”) (No 2012CB517700), and Natural Science Foundation of Jiangsu Province (No BK201106; all to Bi-cheng LIU, Principle Investigator).
* To whom correspondence should be addressed.
E-mail liubc64@163.com
Received 2014-02-12 Accepted 2014-05-26