Review Article

Roles of Inflammasomes in Inflammatory Kidney Diseases

Table 1

Roles of inflammasomes in inflammatory kidney diseases.

DiseaseInflammasomes involvedRoles and potential mechanismReference

Acute kidney injuryNLRP3Nlrp3 gene deletion protected mice from AKI.[143, 144]
ATP-sensitive P2X7 receptor activates the NLRP3 inflammasomes.[145]
Cell debris (histones, HGBM1, etc.) mediated NLRP3 inflammasome activation.[70, 72, 74]

IgA nephropathyNLRP3Nlrp3 deficiency improved renal function and renal injury in a mouse IgAN model.[85]
NLRP3 gene expression was correlated with clinical outcome in IgAN patients.[82]
IgA-immune complexes activated NLRP3 inflammasomes involving ROS production in macrophages, dendritic cells, and renal intrinsic cells.[85]
Generation of ROS and activation of NF-κB lead to NLRP3 activation, which is a key event in IgAN.[84]

Diabetic nephropathyNLRP3Nlrp3-deficient mice are protected against diabetic nephropathy.[88, 89]
Mitochondrial ROS, TLR4 signaling, and NLRP3 inflammasome activation aggravate diabetic nephropathy.[89, 91]
TXNIP activated NLRP3 inflammasomes in podocytes of diabetic nephropathy.[95, 146]
High glucose and LPS activate ROS/TXNIP/NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells.[96]
ATP-P2X4 signaling mediated high glucose-induced activation of NLRP3 inflammasomes.[90]
NLRC4Nlrc4 deficiency resulted in diminished disease progression in diabetic mice. Activation of NF-κB and MAPK pathways was blocked by Nlrc4 deficiency.[98]

Lupus nephritisNLRP1Polymorphism of NLRP1 was related to the pathogenesis of lupus.[119]
NLRP3NLRP3 inflammasomes were activated in podocytes from NZM2328 mice and patients of LN; P2X7/NLRP3 is a key signaling pathway.[110, 111]
Immune complex containing dsDNA induced IL-1β production through NLRP3 inflammasomes.[104, 105]
Lack of NLRP3 enhanced lupus symptom in B6lpr mice by inhibiting TGF target genes.[114]
AIM2AIM2 expression was increased in lupus patients and closely correlated with the severity of disease in SLE patients. AIM2 facilitates the apoptotic DNA-induced lupus damage via arbitrating macrophage functional maturation.[100, 131]
IFI16IFI16 expression was increased in leukocytes but not in kidney biopsies of lupus patients.[129, 131]
Anti-IFI16 antibody titers were higher in lupus patients and inversely correlated with proteinuria.[110]