title: Histamine downregulates the Th1-associated chemokine IP-10 in monocytes and myeloid dendritic cells.
abstract: BACKGROUND
  Histamine is an important mediator of allergic diseases. It modulates the cytokine expression of various subtypes of antigen-presenting cells by four known receptors, H1R-H4R. The effects of histamine on myeloid dendritic cells (mDC) are unclear.
  
  
  METHODS
  Monocytes and mDC were isolated from human PBMC. Histamine receptor expression was evaluated by real-time PCR. Cells were stimulated with histamine and histamine receptor ligands, and restimulated with polyinosinic-polycytidylic acid (poly I:C), and supernatants were analyzed by protein array and ELISA.
  
  
  RESULTS
  Monocytes and mDC express H1R and H2R without significant differences between the two cell types, whereas H4R mRNA was significantly higher in mDC compared with monocytes and H3R mRNA was not detected in any cell type. Prestimulation with histamine caused a significant decrease in poly I:C-induced expression of interferon-γ-induced protein (IP-10) in mDC and monocytes. Stimulation with specific H1R, H2R and H4R agonists and antagonists showed that the observed effect was mediated via H2R and H4R in monocytes and mDC.
  
  
  CONCLUSIONS
  Monocytes and mDC have similar histamine receptor repertoires with regard to H1R, H2R and H3R, but H4R expression is higher on mDC. Histamine stimulation shows similar functional effects on both cell types, i.e., downregulation of TLR3-induced IP-10 production. This might be a new mechanism how histamine fosters a Th2 milieu.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Glatzer
authors.forename: Susanne
authors.initials: S
authors.lastname: Mommert
authors.forename: Brigitta
authors.initials: B
authors.lastname: Köther
authors.forename: Maria
authors.initials: M
authors.lastname: Gschwandtner
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
mesh_terms: D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009928:Organ Specificity; D011070:Poly I-C / Q000494:pharmacology; D061251:Primary Cell Culture; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology; D011968:Receptors, Histamine / Q000235:genetics / Q000276:immunology; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000172:deficiency / Q000235:genetics; D000074040:Receptors, Histamine H4; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D006632:Histamine; D007371:Interferon-gamma; D011070:Poly I-C