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

Kang,Dong Young; Sp,Nipin; Jo,Eun Seong; Rugamba,Alexis; Kim,Hyoung Do; Kim,Il Ho; Park,Jong-Chan; Bae,Se Won; Jang,Kyoung-Jin; Yang,Young Mok

doi:10.3892/mmr.2021.12124

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

Authors:
- Dong Young Kang
- Nipin Sp
- Eun Seong Jo
- Alexis Rugamba
- Hyoung Do Kim
- Il Ho Kim
- Jong-Chan Park
- Se Won Bae
- Kyoung-Jin Jang
- Young Mok Yang
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Affiliations: Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju, North Chungcheong 27478, Republic of Korea, Nara Bio Co., Ltd., Gunsan, Jeollabuk-do 54006, Republic of Korea, Plant Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 34141, Republic of Korea, Department of Chemistry and Cosmetics, Jeju National University, Jeju-si, Jeju-do 63243, Republic of Korea
Published online on: April 27, 2021 https://doi.org/10.3892/mmr.2021.12124
Article Number: 485
Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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