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.

Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling

“…Recently, glucosinolate metabolites have generated a great deal of interest, due to their biological effects, including anti-inflammatory effects [7–10], as well as anti-cancer activity [4,5,21]. For example, BITC (derived from glucotropaeolin) and PITC (derived from gluconasturtiin) have been found to possess anti-cancer [22,23] and anti-inflammatory activities [7,8]. Additionally, SFN, an isothiocyanate derived from hydrolysis of glucoraphanin, is a well-known chemopreventive compound [23] and anti-inflammatory agent [9,10].…”

Cruciferous Vegetables, Isothiocyanates, and Prevention of Bladder Cancer

“…Growth-inhibitory activities of ITCs are associated with cell cycle arrest, induction of apoptosis, inhibition of angiogenesis and invasion [81–86]. PEITC and SF also inhibit inflammatory response, including downregulation of cyclooxygenase-2 (Cox-2) and reduction of prostaglandin E2 level [87, 88]. Toll-like receptor 4 (TLR4) is closely involved in inflammation, and SF (10–20 µM) down regulated TLR4 signaling via thiol-dependent inhibition of its oligomerization in macrophages [89].…”

Sulforaphane and its methylcarbonyl analogs inhibit the LPS-stimulated inflammatory response in human monocytes through modulating cytokine production, suppressing chemotactic migration and phagocytosis in a NF-κB- and MAPK-dependent manner

“…Topical treatment with SF or SFrich broccoli sprout extracts has also been reported in another study to protect against UVR-induced inflammation and edema in SKH-1 hairless mice [17]. The anti-inflammatory abilities of SF and other dietary ITCs have also been subsequently demonstrated in mouse or human skin by several research groups [15,[18][19][20]. However, the inhibitory effects of ITCs on the inflammatory response in activated monocytes isolated from healthy human subjects are not well studied.…”