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Inhibitory Effect of Imiquimod‐Induced Psoriasis‐Like Skin Inflammation in Mice by Histamine H4 Receptor Agonist 4‐Methylhistamine
Author(s) -
Kim C.H.,
Lee J. M.,
Yoo J. K.,
Kim J.S.,
Kim S.U.,
Chang K.T.,
Choo Y.K.
Publication year - 2016
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12420
Subject(s) - psoriasis , foxp3 , agonist , histamine , inflammation , imiquimod , immune system , pharmacology , immunology , medicine , proinflammatory cytokine , atopic dermatitis , receptor , endocrinology , chemistry
Psoriasis is a chronic inflammatory immune‐mediated autoimmune skin disorder. The histamine H4 receptor (H4R) agonist 4‐methylhistamine (4‐ MH ) plays an important role in immunomodulation of inflammatory responses associated with allergic inflammatory diseases. In this study, we investigated the effects of H4R agonist 4‐ MH on the development of imiquimod ( IMQ )‐induced psoriasis‐like skin inflammation in mice and explored the immunoregulatory mechanism involved. The total clinical severity scores were significantly ameliorated by treatment with 4‐ MH (20 mg/kg) and 4‐ MH (40 mg/kg). Histological analysis of the skin revealed that 4‐ MH (20 mg/kg) and 4‐ MH (40 mg/kg) significantly attenuated the psoriatic phenotypes, including epidermal hyperplasis, hyperkeratosis and lymphocytes infiltration. Treatment with 4‐ MH (20 mg/kg) and 4‐ MH (40 mg/kg) led to reductions in the levels of Th1 cytokines ( TNF ‐ α , IFN ‐ α , and IL ‐27) in the serum and dorsal skin, whereas Th17 cytokines levels ( IL ‐17A and IL ‐23) did not change in response to treatment with 4‐ MH (20 mg/kg) and 4‐ MH (40 mg/kg). Furthermore, the number of CD 4 + CD 25 + FoxP3 + regulatory T (Treg) cells was significantly increased by treatment with 4‐ MH (40 mg/kg). Taken together, these results imply that H4R agonist 4‐ MH might be an effective immunomodulatory approach for treatment of patients with psoriasis and the effects may be related to inhibited epidermal alteration, selectively reduced Th1 pro‐inflammatory cytokines, and recruited CD 4 + CD 25 + FoxP3 + Treg cells.