Alleviation of Atopic Dermatitis Lesions by a Benzylideneacetophenone Derivative via the MAPK Signaling Pathway

Abstract

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 (HMC-1 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.

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Funding

This research was supported by a National Research Foundation (NRF) grant funded by the Korean Ministry of Science, ICT and Future Planning (grant no. MRC 2010-0029355).

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Correspondence to Seikwan Oh.

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Sur, B., Kang, S., Kim, M. et al. Alleviation of Atopic Dermatitis Lesions by a Benzylideneacetophenone Derivative via the MAPK Signaling Pathway. Inflammation 42, 1093–1102 (2019). https://doi.org/10.1007/s10753-019-00971-w

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KEY WORDS

  • atopic dermatitis
  • benzylideneacetophenone derivative
  • trimellitic anhydride
  • interleukin-4
  • mitogen-activated protein kinase