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Dehydroxymethylepoxyquinomicin, a novel nuclear factor‐κB inhibitor, prevents inflammatory injury induced by interferon‐γ and histamine in NCTC 2544 keratinocytes
Author(s) -
Cardile Venera,
Libra Massimo,
Caggia Silvia,
Frasca Giuseppina,
Umezawa Kazuo,
Stivala Franca,
Mazzarino Maria Clorinda,
Bevelacqua Ylenia,
Coco Marinella,
Malaponte Grazia
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05375.x
Subject(s) - histamine , viability assay , tumor necrosis factor alpha , microbiology and biotechnology , cytokine , monocyte , mtt assay , pharmacology , western blot , chemistry , in vitro , immunology , medicine , biology , biochemistry , gene
Summary 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.