Hydrogen sulfide modulates high glucose‑induced NLRP3 inflammasome activation in 3T3‑L1 adipocytes

Abstract

Activation of the NACHT leucine rich repeat and pyd domains-containing 3 (NLRP3) inflammasome plays an important role in the initiation of inflammation in adipose tissue in diabetic patients. However, the mechanisms underlying this are not fully understood. Hydrogen sulfide (H2S) has been shown to have anti-inflammatory properties in various cell types. The present study aimed to investigate the effect of H2S on high glucose (HG)-induced NLRP3 inflammasome activation in adipocytes. Adipocytes were differentiated from 3T3-L1 cells and treated with low glucose (LG), HG, H2S donor sodium hydrosulfide (NaHS) or N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone, an inhibitor of the cysteine protease caspase-1. The expression levels of NLRP3, apoptosis-associated speck-like protein containing A CARD (ASC) and caspase-1, and the release of interleukin (IL)-1 beta and IL-18 were measured. The results of the present study indicated that HG increased the expression levels of NLRP3, ASC and cleaved caspase-1, and the release of IL-1 beta and IL-18 in adipocytes. Caspase-1 inhibition abolished HG-induced production of IL-1 beta and IL-18 in adipocytes. Furthermore, NaHS inhibited the expression of NLRP3, ASC and cleaved caspase-1, and the production of IL-1 beta and IL-18 in adipocytes treated with HG. In conclusion, HG may increase and exogenous H2S may inhibit HG-induced NLRP3 inflammasome activation in adipocytes.