Salicylideneamino-2-thiophenol inhibits inflammatory mediator genes (RANTES, MCP-1, IL-8 and HIF-1α) expression induced by tert-butyl hydroperoxide via MAPK pathways in rat peritoneal macrophages

摘要

Salicylideneamino-2-thiophenol (Sal) regulated the redox status and the expression of chemokines induced by tert-butyl hydroperoxide (t-BHP). Sal (100 μM) increased reduced/oxidized glutathione (GSH/GSSG) ratios and thiol (SH) levels by 210 and 157%, respectively, and decreased reactive oxygen species (ROS) levels by 60% in t-BHP-treated macrophages. The inductions of regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8) and hypoxia inducible factor-1α (HIF-1α) by t-BHP (10 μM) were decreased to 250, 80, 80 and 500% by Sal (100 μM), respectively. In the Sal signaling pathway, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and p38 signaling protein modulation were decreased by 67, 69 and 119%, respectively, by Sal at 100 μM. Sal (100 μM) also altered cytosol and nuclear NF-κB protein expression by 169 and 5%, respectively. Sal also attenuated NF-κB nuclear binding activity. Sal thus has a protective effect against t-BHP-induced inflammation and that this, in part, is due to the inhibition of the production of RANTES, MCP-1, IL-8 and HIF-1α via the modulation of the NF-κB and mitogen-activiated protein kinase (MAPK) pathways.