title: Brief report: first identification of H₄ histamine receptor in healthy salivary glands and in focal sialadenitis in Sjögren's syndrome.
abstract: OBJECTIVE
  The conventional H(1) and H(2) histamine receptors have >10,000-fold lower avidity for histamine than H(4) histamine receptor, which has been implicated in autoimmune diseases. This study was undertaken to compare H(4) histamine receptor levels in the salivary glands (SGs) of healthy controls with those in the SGs of patients with primary Sjögren's syndrome (SS).
  
  
  METHODS
  H(4) histamine receptor messenger RNA (mRNA) was analyzed using real-time quantitative polymerase chain reaction, and the receptor protein was examined using immunostaining. Effects of the H(4) histamine receptor agonist ST-1006 on cytokine synthesis by human SG (HSG) cells were analyzed using xMAP technology and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Healthy SGs contained H(4) histamine receptor mRNA. The receptor protein was localized to the acinar and ductal epithelial cells. H(4) histamine receptor agonist stimulated HSG cells to produce the cytokines interleukin-8 and vascular endothelial growth factor. SS patients had low H(4) histamine receptor levels.
  
  
  CONCLUSIONS
  H(1) and H(2) histamine receptor antagonists are not effective in the treatment of autoimmune diseases. However, such antagonists do not affect the newly discovered H(4) histamine receptor. Dendritic cells and lymphocytes are nonprofessional histamine-producing cells, which produce histamine at 100-1,000-fold lower rates than mast cells do. Saliva contains only 0.31-12.4 ng/ml histamine, which is too low to stimulate H(1) or H(2) histamine receptor, but stimulates H(4) histamine receptor half maximally. Our findings show that H(4) histamine receptor is strongly expressed in tubuloacinar SG cells, which emphasizes the role of these cells in the pathogenesis of SS.
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Stegaev
authors.forename: T
authors.initials: T
authors.lastname: Sillat
authors.forename: P
authors.initials: P
authors.lastname: Porola
authors.forename: A
authors.initials: A
authors.lastname: Hänninen
authors.forename: A
authors.initials: A
authors.lastname: Falus
authors.forename: D
authors.initials: D
authors.lastname: Mieliauskaite
authors.forename: E
authors.initials: E
authors.lastname: Buzás
authors.forename: Z
authors.initials: Z
authors.lastname: Rotar
authors.forename: Z
authors.initials: Z
authors.lastname: Mackiewicz
authors.forename: H
authors.initials: H
authors.lastname: Stark
authors.forename: P L
authors.initials: PL
authors.lastname: Chazot
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D012793:Sialadenitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000150:complications*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C418607:HRH4 protein, human; D016209:Interleukin-8; C000610568:N4-(2,6-dichlorobenzyl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D042461:Vascular Endothelial Growth Factor A