title: Phenethyl isothiocyanate inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory responses in mouse skin.
abstract: Phenethyl isothiocyanate (PITC) is the hydrolysis product of the glucosinolate gluconasturtiin in cruciferous vegetables. This study was conducted to determine whether PITC inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the mouse ear. Topical application of 5 nmol of TPA to mouse ears markedly increased the ear weight, expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein, and phosphorylation of the inhibitor of κB (IκB) α, AKT, and extracellular signal-regulated protein kinase (ERK) 1/2 and reduced IκBα protein levels. Pretreatment with PITC (150-450 nmol) significantly suppressed these TPA-induced inflammatory responses. We also determined whether low concentrations of PITC (0.5-5 μmol/L) inhibited lipopolysaccharide (LPS)-stimulated inflammatory responses in Raw264.7 cells. PITC dose-dependently reduced the LPS-induced secretion of nitric oxide, prostaglandin E(2), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, as well as COX-2 and iNOS protein expression. PITC also attenuated LPS-induced increases in iNOS, COX-2, IL- 6, IL-1β, and TNF-α mRNA levels, as well as the promoter-dependent transcriptional activation of the genes for iNOS and COX-2. PITC inhibited LPS-induced IκBα phosphorylation and degradation and subsequently reduced LPS-induced p65 nuclear translocation and the transcriptional activity of nuclear factor-κB (NF-κB), which was accompanied by a reduction in ERK1/2 and AKT phosphorylation. The results of this study demonstrated that PITC effectively inhibits inflammatory responses in vivo and in vitro, which may be mediated via the inhibition of AKT and ERK1/2 activation, leading to subsequent inhibition of the transcriptional activity of NF-κB.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Yeo Myeong
authors.initials: YM
authors.lastname: Lee
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Shree Priya
authors.initials: SP
authors.lastname: Ponnuraj
authors.forename: Jongdai
authors.initials: J
authors.lastname: Kim
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Kim
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha; C073701:Nfkb1 protein, mouse; D009569:Nitric Oxide; C058305:phenethyl isothiocyanate; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate