Reference - Detail
| RRC ID | 54906 |
|---|---|
| Author | Zhang T, Ono K, Tsutsuki H, Ihara H, Islam W, Akaike T, Sawa T. |
| Title | Enhanced Cellular Polysulfides Negatively Regulate TLR4 Signaling and Mitigate Lethal Endotoxin Shock. |
| Journal | Cell Chem Biol |
| Abstract |
Cysteine persulfide and cysteine polysulfides are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. Accumulating evidence has suggested that cysteine persulfides/polysulfides are abundant in prokaryotes and eukaryotes and play important roles in diverse biological processes such as antioxidant host defense and redox-dependent signal transduction. Here, we show that enhancement of cellular polysulfides by using polysulfide donors developed in this study resulted in marked inhibition of lipopolysaccharide (LPS)-initiated macrophage activation. Polysulfide donor treatment strongly suppressed LPS-induced pro-inflammatory responses in macrophages by inhibiting Toll-like receptor 4 (TLR4) signaling. Other TLR signaling stimulants-including zymosan A-TLR2 and poly(I:C)-TLR3-were also significantly suppressed by polysulfur donor treatment. Administration of polysulfide donors protected mice from lethal endotoxin shock. These data indicate that cellular polysulfides negatively regulate TLR4-mediated pro-inflammatory signaling and hence constitute a potential target for inflammatory disorders. |
| Volume | 26(5) |
| Pages | 686-698.e4 |
| Published | 2019-5-16 |
| DOI | 10.1016/j.chembiol.2019.02.003 |
| PII | S2451-9456(19)30037-6 |
| PMID | 30853417 |
| MeSH | Animals Cell Survival / drug effects Extracellular Signal-Regulated MAP Kinases / metabolism Glutathione / chemistry Immunity, Innate / drug effects Interferon-beta / metabolism Lipopolysaccharides / toxicity Macrophages / cytology Macrophages / drug effects Macrophages / metabolism Male Mice Mice, Inbred C57BL Nitrites / metabolism Phosphorylation / drug effects RAW 264.7 Cells Signal Transduction / drug effects* Sulfides / chemical synthesis Sulfides / pharmacology* Toll-Like Receptor 4 / chemistry Toll-Like Receptor 4 / metabolism* Tumor Necrosis Factor-alpha / blood |
| IF | 6.762 |
| Times Cited | 6 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |