Program

PO1-4-42

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

(Background)
 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.
(Method)
 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.
(Results)
 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.
(Conclusion)
 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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