Alleviation of Atopic Dermatitis Lesions by a Benzylideneacetophenone Derivative via the MAPK Signaling Pathway
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ORIGINAL ARTICLE
Alleviation of Atopic Dermatitis Lesions by a Benzylideneacetophenone Derivative via the MAPK Signaling Pathway Bongjun Sur,1 Seungmin Kang,1 Mijin Kim,1 and Seikwan Oh1,2
This experiment was conducted to investigate the effects of a benzylideneacetophenone derivative ((2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one (JC3)) on trimellitic anhydride (TMA)–induced atopic dermatitis (AD)–like symptoms in mice. To induce AD, the dorsal skins of mice were treated with 5% TMA on day 0 and both ears were treated with 5% TMA on day 5 and with 2% TMA from day 6 to day 14. JC3 (1, 5, 10 mg/kg, i.p.) was treated once daily from day 9 to day 14 before TMA treatment. Histological analysis was performed and auricular lymph node weights, ear thicknesses, skin water contents, scratching behaviors, and serum immunoglobulin (IgE) and IFN-γ, and interleukin-4 (IL-4) levels in serum and ear tissues were determined. In addition, the anti-AD activity of JC3 was investigated on phorbol 12-myristate 13-acetate (PMA)–stimulated human mast cells (HMC1 cells) derived from patients. Levels of TNF-α, IL-4, and mitogen-activated protein kinase (MAPK) were investigated after treating cultured cells with JC3. Treating mice with JC3 (10 mg/kg) significantly decreased ear thicknesses, lymph node weights, skin scores, skin water contents, scratching behavior, and IFN-γ, IL-4 cytokine levels, and serum IgE levels. Moreover, treatment with JC3 (10 mg/kg) significantly decreased serum and ear tissues levels of IFN-γ and IL-4 in AD mice. Furthermore, treatment with JC3 at 10 μg/ml reduced TNF-α and IL-4 levels and decreased MAPK phosphorylation in the HMC-1 cells. The results of this study provide a molecular basis for developing new therapeutics for the treatment of various inflammatory diseases, such as, eczema, asthma, and AD.
Abstract—
KEY WORDS: atopic dermatitis; benzylideneacetophenone derivative; trimellitic anhydride; interleukin-4; mitogenactivated protein kinase.
INTRODUCTION Atopic dermatitis (AD) is a skin disease that causes severe recurrent itching [21, 30]. Although previous studies have addressed the pathogenesis of AD, its etiology is not yet understood. AD is characterized by eczema, 1
Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University, Seoul, 07084, South Korea 2 To whom correspondence should be addressed at Department of Molecular Medicine and TIDRC, School of Medicine, Ewha Womans University, Seoul, 07084, South Korea. E-mail: [email protected]
dermatitis and itching, elevated levels of serum immunoglobulin E (IgE), and the infiltrations of immune cells, such as mast cells, eosinophils, neutrophils, and skin lymphocytes [26]. Recently, some authors have suggested the symptoms of AD are associated with elevated levels of type 2 helper T cell type 2 (Th2) cytokines, such as interleukin (IL)-4, IL-5, and IL-13, and the release of IgE from B cells and its binding to mast cells (MCs), which are the major effectors of IgE-mediated hypersensitivity [13]. Infiltration of the u
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