Adiponectin alleviates LPS-induced inflammatory response of microglia through A20/NLRP3/caspase-1 pathway / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To explore the mechanism of adiponectin (APN) on lipopolysaccharide (LPS)-induced microglial inflammatory response. 【Methods】 After APN intervention or/and LPS stimulation, microglia were harvested and divided into control group, APN group, LPS group, and LPS+APN group. The expressions and secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in microglia were detected by q-PCR and ELISA assay, respectively. The expressions of tumor necrosis factor α-induced protein 3 (TNFAIP3/A20), NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and caspase-1 were detected by Western blot. After silencing A20 expression in the microglia, the cells were treated with APN, and the expressions of A20, NLRP3 and caspase-1 were detected by Western blot again. 【Results】 The mRNA transcription levels (P=0.018, P=0.009) and secretion (P=0.000 1, P=0.000 1) of TNF-α and IL-1β in LPS-induced microglia were significantly decreased after APN intervention. Moreover, the expression of A20 was increased while the expressions of NLRP3 and caspase-1 declined in microglia of LPS+ APN group when compared with LPS group (P=0.001, P=0.003, P=0.006). However, the down-regulated expressions of NLRP3 and caspase-1 by APN were reversed by A20 silencing in microglia (P=0.012, P=0.024). 【Conclusion】 APN can inhibit NLRP3 and caspase-1 expressions in microglia by the up-regulated expression of A20 protein.