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)-1β 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-1β and IL-18 in adipocytes. Caspase-1 inhibition abolished HG-induced production of IL-1β and IL-18 in adipocytes. Furthermore, NaHS inhibited the expression of NLRP3, ASC and cleaved caspase-1, and the production of IL-1β 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.