title: Histamine differentially regulates the production of Th1 and Th2 chemokines by keratinocytes through histamine H1 receptor.
abstract: Histamine is a biological amine that plays an important role in allergic responses. However, the involvement of histamine signaling in late allergic responses in the skin is poorly understood. Therefore, we attempted to investigate the involvement of histamine signaling in late allergic responses, especially in keratinocytes (KCs). HaCaT KCs and normal human KCs (NHKs) predominantly expressed histamine H1 receptor (H1R) and H2 receptor (H2R). Histamine suppressed tumor necrosis factor α (TNF-α)- and interferon-γ (IFN-γ)-induced production of CC chemokine ligand 17(CCL17), a type 2 T-helper (Th2) chemokine, by HaCaT KCs. It suppressed the phosphorylation of p38 mitogen-activated protein (MAP) kinase, but not that of extracellular signal-regulated kinases (ERKs), and TNF-α- and IFN-γ-induced nuclear factor κB (NFκB) activity. In contrast, histamine enhanced the production of CXC chemokine ligand 10 (CXCL10), a Th1 chemokine, by TNF-α- and IFN-γ-stimulated HaCaT KCs and NHKs. TNF-α- and IFN-γ-induced CXCL10 production was upregulated by suppression of p38 MAP kinase or NF-κB activity, which could explain histamine involvement. We concluded that histamine suppresses CCL17 production by KCs by suppressing p38 MAP kinase and NF-κB activity through H1R and may act as a negative-feedback signal for existing Th2-dominant inflammation by suppressing CCL17 and enhancing CXCL10 production.
authors.affiliation: Department of Dermatology, University of Tokyo, Tokyo, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komine
authors.forename: Masaru
authors.initials: M
authors.lastname: Karakawa
authors.forename: Hideya
authors.initials: H
authors.lastname: Uratsuji
authors.forename: Shinji
authors.initials: S
authors.lastname: Kagami
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Saeki
authors.forename: Mamitaro
authors.initials: M
authors.lastname: Ohtsuki
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis*; D017931:DNA Primers; D006632:Histamine / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D018925:Chemokines; D017931:DNA Primers; D011969:Receptors, Histamine H1; D006632:Histamine; D011494:Protein Kinases