Salicylideneamino-2-thiophenol inhibits inflammatory mediator genes (RANTES, MCP-1, IL-8 and HIF-1alpha) expression induced by tert-butyl hydroperoxide via MAPK pathways in rat peritoneal macrophages.
Salicylideneamino-2-thiophenol (Sal) regulated the redox status and the expression of chemokines induced by tert-butyl hydroperoxide (t-BHP). Sal (100 microM) 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-1alpha (HIF-1alpha) by t-BHP (10 microM) were decreased to 250, 80, 80 and 500% by Sal (100 microM), 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 microM. Sal (100 microM) also altered cytosol and nuclear NF-kappaB protein expression by 169 and 5%, respectively. Sal also attenuated NF-kappaB 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-1alpha via the modulation of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways.
Chung
Jin
J
Department of Microbiology, School of Dentistry and Research Institute for Oral Biotechnology, Busan, Korea.
Lee
Hwa Sun
HS
Chung
Hae Young
HY
Yoon
Taek Rim
TR
Kim
Hyung Keun
HK
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology*; D020156:Salicylic Acid / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D016328:NF-kappa B; D010636:Phenols; D012333:RNA, Messenger; D012459:Salicylates; D013438:Sulfhydryl Compounds; C532534:salicylideneamino-2-thiophenol; C042983:thiophenol; D020122:tert-Butylhydroperoxide; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D020156:Salicylic Acid