title: Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte-derived Langerhans cells in patients with atopic dermatitis.
abstract: We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte-derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2-signaled enhancement, peptidoglycan (PGN)-enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen-activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T-helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD.
authors.affiliation: Department of Dermatology, Saitama Medical University, Saitama, Japan.|Allergology Center, Saitama Medical University, Saitama, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Miyano
authors.affiliation: Allergology Center, Saitama Medical University, Saitama, Japan.|Department of Immunology, Saitama Medical University, Saitama, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Department of Dermatology, Saitama Medical University, Saitama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsuchida
authors.affiliation: Department of Dermatology, Saitama Medical University, Saitama, Japan.|Allergology Center, Saitama Medical University, Saitama, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000378:metabolism*; D054422:Chemokine CCL22 / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D010457:Peptidoglycan / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; C418607:HRH4 protein, human; D007211:Indoles; D010457:Peptidoglycan; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Langerhans cells; atopic dermatitis; chemokines; histamine 4 receptor antagonist; peptidoglycan