Inhibition of CEBPB Attenuates Lupus Nephritis via Regulating Pim-1 Signaling.

Systemic lupus erythematosus (SLE) is an autoimmune disease leading to inflammatory damage in multiple target organs, and lupus nephritis (LN) is one of the most life-threatening organ manifestations. CCAAT/enhancer-binding protein (CEBPB) regulates the NLRP3 inflammasome and is involved in the pathogenesis of SLE. However, the role and mechanism of CEBPB in LN remains unclear. MRL/lpr mice and lipopolysaccharides (LPS) combined with adenosine triphosphate- (ATP-) treated glomerular podocytes were used as models of LN and , respectively. , we investigated the expressions of CEBPB during the development of MRL/lpr mice. Then we assessed the effect of CEBPB inhibition on renal structure and function through injecting sh lentivirus into MRL/lpr mice. , glomerular podocytes were treated with -OE and si to explore the relation between and . The progression of LN in mice was associated with the increased level of CEBPB, and the inhibition of CEBPB ameliorated renal structure impairments and improved renal function damage associated with LN. Knockdown of could suppress the activation of NLRP3 inflammasome and the secretion of IL-1 and IL-6. Furthermore, the knockdown of could inhibit NLRP3 inflammasome activation and pyroptosis via binding to promoter to downregulate its expression, and the overexpression of reversed the effects of deficiency. The regulation of on facilitated pyroptosis by activating NLRP3 inflammasome, thereby promoting the development of LN.