title: Histamine H4 receptor in oral lichen planus.
abstract: OBJECTIVE
  Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines.
  
  
  METHODS
  Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes.
  
  
  RESULTS
  H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts.
  
  
  CONCLUSIONS
  Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.
authors.affiliation: Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Oral Pathology, University of Helsinki, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Salem
authors.forename: A
authors.initials: A
authors.lastname: Al-Samadi
authors.forename: V
authors.initials: V
authors.lastname: Stegajev
authors.forename: H
authors.initials: H
authors.lastname: Stark
authors.forename: R
authors.initials: R
authors.lastname: Häyrinen-Immonen
authors.forename: M
authors.initials: M
authors.lastname: Ainola
authors.forename: J
authors.initials: J
authors.lastname: Hietanen
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D017676:Lichen Planus, Oral / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine; D007371:Interferon-gamma
keywords: cytokines; histamine H4 receptor; mast cells; oral lichen planus; oral pathology