The effect of mild electrical stimulation with heat shock on imiquimod-induced psoriasis-like inflammation

[Speaker] Yu Tsurekawa:1,2
[Co-author] Misaki Morita:1,2, Masataka Moriuchi:1,2, Yoshio Nakano:1,2, Mariam Piruzyan:1,2, Masafumi Takada:1, Sanako Fukami:1, Mary Ann Suico:1, Tsuyoshi Shuto:1, Hirofumi Kai:1,2
1:Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Japan, 2:Program for Leading Graduate Schools HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program, Kumamoto University, Japan

 Physical stimulation modulates intracellular signaling pathways in various types of cells. Our laboratory has shown that optimized mild electrical stimulation (MES, 0.1-ms pulse width, 55-pulse per second; pps) with heat shock (HS, 42oC) has therapeutic effect on mouse model of type 2 diabetes and chronic kidney disease. In clinical studies, MES+HS treatment showed the tolerability and beneficial effects on type 2 diabetes and metabolic syndrome. DNA microarray analysis revealed changes in gene expression patterns of MES+HS-treated mice skin. However, the pathophysiological relevance of MES+HS-dependent gene alteration in skin is unknown. To determine the effect of MES+HS in pathological condition on the skin, we assessed whether MES+HS ameliorates psoriasis-like skin inflammation.
 Here, we generated imiquimod-induced psoriasis mouse model and treated them with MES+HS. Mice received a daily topical dose of 15 mg of imiquimod cream (beselna cream 5%) on the right ear for 8 days, and were treated with MES+HS for 10 min at 1.5 hr before application of imiquimod. For HS, electrodes were heated to 42oC. Skin thickening was measured with a caliper. Skin tissues of mice were collected for analysis of inflammation-related gene expression by quantitative RT-PCR.
 MES+HS treatment significantly decreased imiquimod-induced ear swelling and the expression of keratinocyte proliferation markers. Furthermore, MES+HS treatment inhibited the expression of psoriasis-associated inflammatory molecules such as IL-17A and antimicrobial proteins in the skin. Importantly, MES+HS also suppressed IL-17A-induced antimicrobial proteins expression in keratinocyte HaCaT cells.
 Our study shows that MES+HS treatment improves imiquimod-induced psoriasis. MES+HS treatment may provide a novel therapy for psoriasis-like skin inflammation.

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