Understanding the role of iron/heme metabolism in the anti‑inflammatory effects of natural sulfur molecules against lipopolysaccharide‑induced inflammation

Kang,Dong Young; Bae,Se Won; Jang,Kyoung-Jin

doi:10.3892/mmr.2025.13542

Understanding the role of iron/heme metabolism in the anti‑inflammatory effects of natural sulfur molecules against lipopolysaccharide‑induced inflammation

Authors:
- Dong Young Kang
- Se Won Bae
- Kyoung-Jin Jang
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Affiliations: Department of Immunology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju, North Chungcheong 27478, Republic of Korea, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of Korea, Department of Integrative Biological Sciences and Industry, College of Life Science, Sejong University, Seoul 05006, Republic of Korea
Published online on: April 17, 2025 https://doi.org/10.3892/mmr.2025.13542
Article Number: 177
Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Iron transport and heme synthesis are essential processes in human metabolism, and any dysregulation in these mechanisms, such as inflammation, can have deleterious effects. Lipopolysaccharide (LPS)‑induced inflammatory responses can result in a number of adverse effects, including cancer. Natural mineral sulfur, methylsulfonylmethane (MSM) and nontoxic sulfur (NTS) suppress inflammatory responses. The present study hypothesized that MSM and NTS may inhibit LPS‑induced inflammatory responses in THP‑1 human monocytes. Reverse transcription‑quantitative PCR and western blotting assays were performed to analyze the molecular signaling pathways associated with sulfur‑treated and untreated cells. A comet assay was used to evaluate DNA damage, flow cytometry was performed to analyze cell surface receptors and chromatin immunoprecipitation was used to examine molecular interactions. Notably, LPS‑induced inflammation increased iron/heme metabolism, whereas MSM and NTS inhibited this effect. Furthermore, LPS treatment activated the Toll‑like receptor 4/NF‑κB signaling axis, which was downregulated by NTS and MSM. These sulfur compounds also suppressed the nuclear accumulation of LPS‑induced NF‑κB, which could induce the production of proinflammatory cytokines, such as TNF‑α, IL‑1β and IL‑6. Finally, MSM and NTS inhibited LPS‑induced reactive oxygen species generation and DNA damage in THP‑1 monocytic leukemia cells. These results suggested that natural sulfur molecules may be considered promising candidates for anti‑inflammation studies.

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