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

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.