The Role of Exogenous Hydrogen Sulfide in Free Fatty Acids Induced Inflammation in Macrophages

Abstract

Background: This study aimed to investigate whether exogenous hydrogen sulfide (H₂S) can protect the RAW264.7 macrophages against the inflammation induced by free fatty acids (FFA) by blunting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. Methods: RAW264.7 macrophages were exposed to increasing concentrations of FFA for up to 3 days to induce FFA-induced inflammation. The cells were pretreated with NaHS (a donor of H₂S) before exposure to FFA. Cell viability, cell apoptosis, TLR4, NF-κB, NLRP3 inflammasome, IL-1β, IL-18 and cleaved caspase-3 expression were measured by a combination of MTT assay, ELISA, and immunoblotting. Results: H₂S attenuated FFA-induced cell apoptosis, and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL- 1β, IL-18 and caspase-3. In addition, H₂S inhibited the FFA-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. Conclusion: The present study demonstrated for the first time that H₂S appears to suppress FFA-induced macrophage inflammation and apoptosis by inhibiting the TLR4/ NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H₂S might possess potential in the treatment of diseases resulting from FFA overload like insulin resistance and type diabetes.

Exogenous Hydrogen Sulfide Alleviates-Induced Intracellular Inflammation in HepG2 Cells

“…Original magnifcation, 200 × . [32][33][34]. Here, this study provides the first evidence of exogenous NaHS observably suppressed the expression of NLRP3 inflammasome in PA-induced HepG2 cells.…”

Diallyl trisulfide, a H2S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H2S and cystathionine‐gamma‐lyase

“…H 2 S, previously regarded primarily as an environmental hazard and toxic gas, has recently been recognized as the third gasotransmitter after carbon monoxide (CO) and nitric oxide (NO; Szabo, ). H 2 S has become a focus of researches because of its role in various biological processes, such as neuronal health (Paul & Snyder, ), cardiovascular health, immune response (Yuan, Shen, & Kevil, ), and inflammation (Luo et al, ). Besides, H 2 S has also been reported to regulate cell cycle, proliferation, autophagy, apoptosis, and oxidative stress in malignant tumors (Hellmich & Szabo, ).…”

<p>Ursolic Acid Protects Against Proliferation and Inflammatory Response in LPS-Treated Gastric Tumour Model and Cells by Inhibiting NLRP3 Inflammasome Activation</p>

“…NF-κB plays a critical role in regulating inflammation and serves as the first signal in the activation of the NLRP3 inflammasome. 12 , 39 – 41 Previous studies demonstrated that NF-κB inhibition led to a remarkable reduction of NLRP3 expression. 33 We found that blocking NF-κB activation with the NF-κB inhibitor BAY-117082 could downregulate NLRP3 expression in BGC-823 cells.…”