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 (H 2 S) has been shown to have anti-inflammatory properties in various cell types. The present study aimed to investigate the effect of H 2 S on high glucose (HG)-induced NLRP3 inflammasome activation in adipocytes. Adipocytes were differentiated from 3T3-L1 cells and treated with low glucose (LG), HG, H 2 S 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 H 2 S may inhibit HG-induced NLRP3 inflammasome activation in adipocytes.

Hydrogen Sulfide Plays an Important Role by Influencing NLRP3 inflammasome

“…In conclusion, H 2 S inhibits HG-induced inflammation of human retinal pigment epithelial cells through inhibiting NLRP3 inflammasome 85 . In HG-induced 3T3‑L1 adipocytes, H 2 S has the effect similar to the above 86 . H 2 S has therapeutic effect on diabetes through inhibiting NLRP3 inflammasome.…”

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

“…Effect of H 2 S on the expression of the NLPR3 inflammasome in placental cells. Our previous study demonstrated that the expression of the NLPR3 inflammasome decreases via H 2 S in adipocytes (29). To investigate the role of H 2 S in the regulation of the NLPR3 inflammasome in placenta, placental cells were cultured and treated with H 2 S donor NaHS or H 2 S precursor L-cysteine.…”

“…Known as 'the third endogenous gaseous signaling transmitter', hydrogen sulfide (H 2 S) exerts biological functions, including anti-inflammatory, anti-oxidative stress and anti-apoptosis (27,28). Our previous study demonstrated that H 2 S suppresses activation of the NLPR3 inflammasome in adipocytes (29). Teng et al (30) reported that H 2 S concentration significantly decreases in parturient women with GDM, suggesting that decreasing H 2 S may be involved in the pathogenesis of GDM.…”

NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

“…Hyperglycaemia can stimulate NLRP3 inflammasome activation in multiple cell types, including THP-1-derived macrophages, 3T3-L1 mature adipocytes and human adipose tissue [102][103][104][105][106][107]. Both caspase-1 and thioredoxin-interacting protein (TXNIP) expression are increased in ob/ob mice.…”