Hydrogen sulfide attenuates cigarette smoke‑induced pyroptosis through the TLR4/NF‑κB signaling pathway

Abstract

Pyroptosis, a type of programmed cell death mediated by caspases‑1 or ‑11, may play an important role in airway epithelial injury and airway remodeling, thereby promoting the occurrence of asthma and chronic obstructive pulmonary disease (COPD). Studies have suggested that hydrogen sulfide (H₂S) plays a protective role against COPD by inhibiting the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The present study established a rat model of cigarette smoke (CS)‑induced COPD to observe the effects of H₂S on cell pyroptosis. A 16HBE cell model was also used to further examine the effects of H₂S on the Toll‑like receptor 4 (TLR4)/NF‑κB signaling pathway is affected by, and to determine the underlying mechanisms. The results revealed that cell pyroptosis was significantly promoted in the model of CS‑induced COPD. The cellular experiments also revealed that CS induced the pyroptosis of the cells in a NLRP3/gasdermin D (GSDMD)‑dependent manner. In addition, H₂S significantly attenuated the effects of CS extract (CSE) on pyroptosis, cell viability and the expression levels of pyroptosis‑related proteins, indicating that H₂S inhibited pyroptosis by decreasing NLRP3 expression and promoting GSDMD activation. It was also identified that CSE activated TLR4 protein in 16HBE cells, while this was inhibited by H₂S. Furthermore, TLR4 and NF‑κB overexpression significantly abolished the effects of H₂S on cell pyroptosis. On the whole, the findings of the present study demonstrate the role of pyroptosis in the development of COPD and provide an experimental basis for the use of H₂S and drugs targeting the TLR4/NF‑κB pathway to exert protective effects against COPD.