The emerging role of the inflammasome in kidney diseases

Abstract

Purpose of review This review focuses on the latest data that elucidates the role of the NLRP3 inflammasome in kidney diseases. Recent findings The NLRP3 inflammasome is not limited by traditional microbial stimuli of innate immunity and its connection with autophagy, apoptosis, fibrosis, and pro-inflammatory cytokines has broader implications for a variety of kidney diseases. In a wide spectrum of glomerular and tubulointerstitial diseases, the NLRP3 inflammasome is upregulated in both classical immune cells such as infiltrating macrophages and resident dendritic cells as well as in renal tubular epithelial cells, and even podocytes. Inhibition of the NLRP3 inflammasome ameliorates renal injury in a variety of animal models. Interestingly, this extends to models of proteinuria, which suggests that the deleterious effect of albuminuria on the proximal tubular epithelium and podocytes is, in part, mediated by inflammasome activation. Summary Recent studies in animal models, and still limited studies in humans, suggest a broad role for inflammasome activation in renal disease. Surprisingly, individual components of the inflammasome, independent of inflammasome activation, may also contribute to progressive renal injury. Additional, studies are needed to define the relative importance of the inflammasome in specific diseases and the therapeutic opportunities afforded by targeting the inflammasome.

Megalin/Cubulin-Lysosome-mediated Albumin Reabsorption Is Involved in the Tubular Cell Activation of NLRP3 Inflammasome and Tubulointerstitial Inflammation

“…Emerging evidence suggests an important role for the NLRP3 inflammasome in the pathogenesis of acute and chronic inflammation and tissue remodeling in the kidney (31). Notably, up-regulation of the NLRP3 inflammasome was demonstrated in both classical immune cells, such as resident dendritic cells and infiltrating macrophages, and podocytes and tubule epithelial cells in a wide range of glomerular and tubulointerstitial diseases (10). Previously, we demonstrated that proteinuria caused NLRP3 inflammasome activation in the proximal tubules in an albumin-overload model (12).…”

Mangiferin Attenuate Sepsis-Induced Acute Kidney Injury via Antioxidant and Anti-Inflammatory Effects

“…Renal inflammation is a universal response to infectious and noninfectious triggers [39]. Evolving data suggest that the inflammasome IL-1/18 axis contributes to acute and chronic inflammation and tissue remodeling in the kidney [40]. Our study defined the relative importance of the inflammasome in specific sepsis-induced AKI and suggested further study to get the therapeutic opportunities afforded by targeting the inflammasome.…”

Current Opinion in the Treatment of Diabetic Nephropathy

“…28 It has been well summarized the recent findings: the Nlrp3 inflammasome is not limited by the traditional microbial stimuli of innate immunity and its connection with autophagy, apoptosis, fibrosis, and pro-inflammatory cytokines has broader implications for a variety of kidney diseases. 29 In a wide spectrum of glomerular and tubulointerstitial diseases, the Nlrp3 inflammasome is upregulated in both classical immune cells such as infiltrating macrophages and resident dendritic cells as well as in renal tubular epithelial cells, and even podocytes. 29 Inhibition of the Nlrp3 inflammasome ameliorates renal injury in a variety of animal models.…”

“…29 In a wide spectrum of glomerular and tubulointerstitial diseases, the Nlrp3 inflammasome is upregulated in both classical immune cells such as infiltrating macrophages and resident dendritic cells as well as in renal tubular epithelial cells, and even podocytes. 29 Inhibition of the Nlrp3 inflammasome ameliorates renal injury in a variety of animal models. 29 The deleterious effect of albuminuria on the proximal tubular epithelium and podocytes is, in part, mediated by inflammasome activation.…”

“…29 Inhibition of the Nlrp3 inflammasome ameliorates renal injury in a variety of animal models. 29 The deleterious effect of albuminuria on the proximal tubular epithelium and podocytes is, in part, mediated by inflammasome activation. 29 Therefore, developing strategies to target Nlrp3 inflammasome in diabetic nephropathy are warranted.…”