Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-23623-9
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Funding
- Japan Society for the Promotion of Science
- Lydia O'leary Memorial Pias Dermatological Foundation
- GlaxoSmithKline research grant
- Novartis Pharmaceuticals research grant
- Mochida Memorial Foundation
- Uehara Memorial Foundation
- Nakatomi Foundation
- Takeda Science Foundation
- LEO Pharma Research Foundation
- Grants-in-Aid for Scientific Research [16K19744] Funding Source: KAKEN
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The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation. Topical MaR1 reduced the ear swelling response as seen in histological findings. RT-PCR and flow cytometry analyses revealed MaR1 had no inhibitory effect on IL-23, but MaR1 suppressed IL-17A production by gamma delta TCRmid+ and CD4(+) cells in the skin. These inhibitory effects were also observed in a subcutaneous IL-23-injected psoriasis model. MaR1 downmodulated IL-23 receptor (IL-23R) expression by suppressing retinoic acid-related orphan receptor gamma t (ROR gamma t) expression and internalization in a clathrin-dependent manner in gamma delta TCRmid+ and CD4(+) cells. These results lead to assumptions that topical MaR1 may be a new therapeutic agent for psoriasis and other IL-17-mediated cutaneous inflammatory diseases.
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