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

Abstract

Janus kinase 2 (JAK2) and STAT3 signaling is considered a major pathway in lipopolysaccharide (LPS)-induced inflammation. Toll-like receptor 4 (TLR-4) is an inflammatory response receptor that activates JAK2 during inflammation. STAT3 is a transcription factor for the pro-inflammatory cytokine IL-6 in inflammation. Sulfur is an essential element in the amino acids and is required for growth and development. Non-toxic sulfur (NTS) can be used in livestock feeds as it lacks toxicity. The present study aimed to inhibit LPS-induced inflammation in C2C12 myoblasts using NTS by regulating TLR-4 and JAK2/STAT3 signaling via the modulation of IL-6. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium 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 enzyme-linked immunosorbent assays were used to determine the binding activity of proteins. The results indicated that NTS demonstrated a protective effect against LPS-induced cell death and inhibited LPS-induced expression of TLR-4, JAK2, STAT3 and IL-6. In addition, NTS inhibited the expression of nuclear phosphorylated-STAT3 and its binding to the IL-6 promoter. Therefore, NTS may be a potential candidate drug for the treatment of inflammation.