title: Inhibitory Effect of Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice by Histamine H4 Receptor Agonist 4-Methylhistamine.
abstract: 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 CD4(+) CD25(+) 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 CD4(+) CD25(+) FoxP3(+) Treg cells.
authors.affiliation: College of Medicine, Dongguk University, Goyang, Korea.
authors.forename: C-H
authors.initials: CH
authors.lastname: Kim
authors.affiliation: College of Medicine, Dongguk University, Goyang, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, CHA University, Goyang-si, Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Yoo
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea.
authors.forename: J-S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea.
authors.forename: S-U
authors.initials: SU
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Korea.
authors.forename: K-T
authors.initials: KT
authors.lastname: Chang
authors.affiliation: Department of Biological science, College of Natural Sciences, Wonkwang University, Iksan, Korea.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Choo
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008761:Methylhistamines / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C418607:HRH4 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D008761:Methylhistamines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C025566:4-methylhistamine; D000077271:Imiquimod