Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling.

Janus kinase 2 (JAK2) and STAT3 signaling is considered a major pathway in lipopolysaccharide (LPS)­induced inflammation. Toll­like receptor 4 (TLR­4) is an inflammatory response receptor that activates JAK2 during inflammation. STAT3 is a transcription factor for the pro­inflammatory cytokine IL­6 in inflammation. Sulfur is an essential element in the amino acids and is required for growth and development. Non­toxic sulfur (NTS) can be used in livestock feeds as it lacks toxicity. The present study aimed to inhibit LPS­induced inflammation in C2C12 myoblasts using NTS by regulating TLR­4 and JAK2/STAT3 signaling via the modulation of IL­6. The 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay was conducted to analyze cell viability and reverse transcription polymerase chain reaction and western blotting performed to measure mRNA and protein expression levels. Chromatin immunoprecipitation and enzyme­linked immunosorbent assays were used to determine the binding activity of proteins. The results indicated that NTS demonstrated a protective effect against LPS­induced cell death and inhibited LPS­induced expression of TLR­4, JAK2, STAT3 and IL­6. In addition, NTS inhibited the expression of nuclear phosphorylated­STAT3 and its binding to the IL­6 promoter. Therefore, NTS may be a potential candidate drug for the treatment of inflammation.