Histamine H4 receptor in oral lichen planus

• Published in: Oral diseases Vol. 21; no. 3; pp. 378 - 385
• Main Authors: Salem, A, Al-Samadi, A, Stegajev, V, Stark, H, Häyrinen-Immonen, R, Ainola, M, Hietanen, J, Konttinen, YT
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01-04-2015; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Aged, 80 and over; Autoimmune diseases; Cell Count; Cell Line; Cytokines; Dentistry; Epithelial Cells - metabolism; Female; Histamine; Histamine - pharmacology; histamine H4 receptor; Humans; Interferon-gamma - pharmacology; Lichen Planus, Oral - genetics; Lichen Planus, Oral - metabolism; Lichen Planus, Oral - pathology; Male; mast cells; Mast Cells - pathology; Mast Cells - physiology; Middle Aged; Oral diseases; oral lichen planus; oral pathology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Histamine - genetics; Receptors, Histamine - metabolism; Receptors, Histamine H4; T cell receptors; Transcription, Genetic - drug effects; Tumor Necrosis Factor-alpha - pharmacology; Young Adult; cytokines; mast cells; oral lichen planus; oral pathology; histamine H4 receptor
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12290

Objectives
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 (H4Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T‐cell cytokines.
Materials and 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
H4R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4R agonist at nanomolar levels led to a rapid internalization of H4Rs, whereas high histamine concentration and interferon‐γ decreased HRH4‐gene transcripts.
Conclusion
Healthy oral epithelial cells are equipped with H4R, 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 H4R. Cell culture experiments suggest a rapid H4R stimulation‐dependent receptor internalization and a slow cytokine‐driven decrease in H4R synthesis. H4R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.