Exogenous hydrogen sulfide mitigates NLRP3 inflammasome-mediated inflammation through promoting autophagy via AMPK-mTOR pathway

Abstract

The aim of this study was to investigate whether exogenous hydrogen sulfide (H 2 S) could mitigate NLRP3 inflammasome-mediated inflammation through promoting autophagy via the AMPK-mTOR pathway in L02 cells. L02 cells were stimulated with different concentrations of oleic acid (OA), then cell viability and the protein expression of NLRP3 and pro-caspase-1 were detected by MTT and western blot, respectively, to determine appropriate OA concentration in this study. The cells were divided into four groups: the cells in the control group were cultured with RPMI-1640 for 24.5 h; the cells in the OA group were cultured with RPMI-1640 for 0.5 h, then were stimulated with 1.2 mmol/l OA for 24 h; the cells in the NaHS+OA group were pretreated with sodium hydrogen sulfide (NaHS, a donor of H 2 S) for 0.5 h before exposure to OA for 24 h; and the cells in the NaHS group were treated with NaHS 0.5 h, then were cultured with RPMI-1640 for 24 h. Subsequently, the cells in every group were collected and the protein expression of NLRP3, procaspase-1, cleaved caspase-1, P62, LC3, Beclin1, T-AMPK, P-AMPK, T-mTOR, P-mTOR and the level of IL-1β were detected by western blot and ElISA, respectively. Exogenous H 2 S reduced the level of NLRP3, caspase-1, P62, IL-1β and the ratio of P-mTOR/T-mTOR induced by OA and increased the ratio of LC3 II/I and the protein expression of Beclin1 suppressed by OA. This study demonstrates for the first time that H 2 S might suppress NLRP3 inflammasome-mediated inflammation induced by OA through promoting autophagy via the AMPK-mTOR pathway. It provides a theoretical basis for the further study of the anti-inflammatory mechanism of H 2 S.

The Role of the Interplay Between Autophagy and NLRP3 Inflammasome in Metabolic Disorders

“…Targeting the effect of autophagy on NLRP3 with oral small molecule compound BBR might improve insulin resistance. Similar to the above results, our previous studies have shown that enhancing autophagy by hydrogen sulfide (H 2 S) suppresses NLRP3 inflammasome through AMPK-mTOR pathway in L02 cells induced by oleic acid ( Wang et al, 2019 ). AMPK-mTOR pathway is an important signaling pathway for the interaction between autophagy and NLRP3 inflammasome.…”

Hydrogen Sulfide Plays an Important Role by Influencing NLRP3 inflammasome

“…3-MA, an autophagy inhibitor, could counteract the effect of H2S, suggesting that autophagy mediated the effect of H 2 S on NLRP3 inflammasome-mediated inflammation. In addition, compound C, an AMPK inhibitor, could inhibit autophagy and counteract the anti-inflammatory effect of exogenous H 2 S. In summary, exogenous H 2 S inhibited NLRP3 inflammasome-mediated inflammation of hepatocytes through promoting autophagy via AMPK/mTOR pathway (Figure 4) [41,42]. Through consulting a large number of related literatures, we found that exogenous H2S could inhibit endoplasmic reticulum stress (ERS) in many diseases [28], and there was interaction between ERS and NLRP3 inflammasome [43], so whether exogenous H 2 S can inhibit NLRP3 inflammasome-mediated inflammatory response through ERS needs further study.…”

Hydrogen Sulfide Plays an Important Role in Diabetic Cardiomyopathy

“…A chronic, low-level state of systemic and sterile inflammation is an important feature of DCM (Sharma et al, 2018 ). The NLRP3 inflammasome is an important complex protein that mediates inflammation (Wang H. et al, 2019 ). Studies showed that suppressing NLRP3 notably improved DCM (Ye et al, 2017 ).…”