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- Title
Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, prevents inflammatory injury induced by interferon-γ and histamine in NCTC 2544 keratinocytes.
- Authors
Cardile, Venera; Libra, Massimo; Caggia, Silvia; Frasca, Giuseppina; Umezawa, Kazuo; Stivala, Franca; Mazzarino, Maria Clorinda; Bevelacqua, Ylenia; Coco, Marinella; Malaponte, Grazia
- Abstract
1. The novel nuclear factor (NF)-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) is a derivative of the antibiotic epoxyquinomicin C from Amycolatopsis sp. that has been found to inhibit tumour necrosis factor (TNF)-α-induced activation of NF-κB by suppressing nuclear translocation of NF-κB. The aim of the present study was to determine the effects of DHMEQ on interferon (IFN)-γ- and histamine-activated NCTC 2544 keratinocytes. 2. Keratinocytes were stimulated or not with 200 U/mL IFN-γ and 10−4 mol/L histamine in the absence or presence of different concentrations of DHMEQ (1, 5 and 10 μg/mL) or hydrocortisone (10−5 mol/L), which was used as a reference anti-inflammatory drug. After 48 h, each sample was tested for the presence of intercellular adhesion molecule (ICAM)-1 by western blot analysis, as well as for the release of monocyte chemoattractant protein (MCP)-1, RANTES and interleukin (IL)-8 using specific sandwich ELISAs. To verify the effect of DHMEQ on cell viability of non-stimulated NCTC 2544 keratinocytes, the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. 3. The results showed that 10 μg/mL DHMEQ potently inhibited ICAM-1 production (by 50%), as well as the release of MCP-1 (to 25% of control), RANTES (to 5% of control) and IL-8 (to 2% of control). The results of the MTT assay indicated that DHMEQ has no effect on cell viability. 4. In conclusion, DHMEQ inhibits the IFN-γ- and histamine-induced activation of the keratinocyte cell line NCTC 2544. The anti-inflammatory effects of DHMEQ could be exploited by applying the drug topically alone or in combination with sub-toxic concentrations of anti-inflammatory drugs to producer a synergistic effect.
- Subjects
KERATINOCYTES; INFLAMMATORY mediators; TUMOR necrosis factors; ANTIVIRAL agents; ANTIBIOTICS
- Publication
Clinical & Experimental Pharmacology & Physiology, 2010, Vol 37, Issue 7, p679
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/j.1440-1681.2010.05375.x