title: Inhibitory action of salicylideneamino-2-thiophenol on NF-κB signaling cascade and cyclooxygenase-2 in HNE-treated endothelial cells.
abstract: In the present study, the anti-inflammatory effect of salicylideneamino-2-thiophenol (SAL-2), a derivative of salicylate, on a potent oxidant 4-hydroxynonenal (HNE)-induced oxidative stress was investigated using rat prostate endothelial (YPEN-1) cells. We focused on anti-inflammatory activity of SAL-2 which was determined by its ability to suppress COX-2 and iNOS gene expression through suppression of NF-κB and redox regulation. We found that SAL-2 effectively inhibited HNE-induced reactive species generation, while upregulated GSH/GSSG ratio. Prostagrandin (PG) E2 production stimulated by arachidonic acid was suppressed by SAL-2. SAL-2 also downregulated COX-2 and iNOS expression induced by HNE, but salicylate did not. We found that SAL-2 inhibited HNE-mediated IKK phosphorylation, IκBα degradation and nuclear translocation of p65 which are linked to NF-κB activation. Furthermore, SAL-2 inhibited HNE-induced activation of mitogen-activated protein kinases. Collectively, SAL-2 inhibited COX-2 and iNOS gene expression through suppression of NF-κB leading to the inhibition of PGE2 synthesis. Based on these data, we propose that with its combined effect on strong anti-oxidant and anti-inflammatory action, SAL-2 can be a potent anti-inflammatory agent for treatment of inflammatory-related diseases.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan, 609-735, South Korea.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.forename: Bokyung
authors.initials: B
authors.lastname: Sung
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Jang
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012459:Salicylates; D013438:Sulfhydryl Compounds; C532534:salicylideneamino-2-thiophenol; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C027576:4-hydroxy-2-nonenal