title: Histamine down-regulates IL-27 production in antigen-presenting cells.
abstract: Histamine is a potent mediator in allergic inflammation with immunomodulatory properties. Since histamine was described to inhibit IL-12 production in human APCs, we hypothesized that also the expression of IL-27, a newly described member of the IL-12 family, which is present in inflammatory skin lesions, is modulated by histamine. Stimulation of human monocytes with histamine resulted in significant reduction of TLR ligand-induced IL-27 production in human monocytes. IL-27 subunits, p28 and EBI3, were down-regulated at the mRNA and protein level, whereas other cytokines, such as IL-6, IL-10, and TNF-α, were not influenced. Studies with histamine receptor-specific agonists and antagonists showed that the down-regulation of IL-27 was mediated via H(2)R and H(4)R but not H(1)R and H(3)R. Human KCs treated with supernatants of histamine-prestimulated monocytes induced significantly less CXCL10 than supernatants containing high levels of IL-27. DCs from H(4)R(-/-) mice responded to TLR simulation with higher IL-27 production as compared with WT mice. The down-regulation of IL-27 by histamine might be a new mechanism in the pathogenesis of inflammatory skin diseases, in particular, if increased concentrations of histamine are present at sites of inflammation, such as in chronic eczema and psoriasis.
authors.affiliation: Hannover Medical School, Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover, Germany. maria_gschwandtner@gmx
authors.forename: Maria
authors.initials: M
authors.lastname: Gschwandtner
authors.forename: Hannah
authors.initials: H
authors.lastname: Bunk
authors.forename: Brigitta
authors.initials: B
authors.lastname: Köther
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thurmond
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumer
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011968:Receptors, Histamine / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D017442:Histamine Agonists; C486767:Il27 protein, mouse; D015850:Interleukin-6; D007378:Interleukins; C464565:MYDGF protein, human; D012333:RNA, Messenger; D011968:Receptors, Histamine; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D006632:Histamine; D007371:Interferon-gamma