{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:14:07Z","timestamp":1774674847378,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,10,8]],"date-time":"2014-10-08T00:00:00Z","timestamp":1412726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Oral lichen planus (<jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content>) is an autoimmune disease characterized by a band\u2010like T\u2010cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high\u2010affinity histamine H<jats:sub>4<\/jats:sub> receptors (H<jats:sub>4<\/jats:sub>Rs) are downregulated in <jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content> by high histamine concentrations and proinflammatory T\u2010cell cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real\u2010time polymerase chain reaction of tissue samples and cytokine\u2010stimulated cultured <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>\u201025 and primary human oral keratinocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>H<jats:sub>4<\/jats:sub>R immunoreactivity was weak in <jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content> and characterized by mast cell (<jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>) hyperplasia and degranulation. In contrast to controls, H<jats:sub>4<\/jats:sub>R immunostaining and <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> counts were negatively correlated in <jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content> (<jats:italic>P\u00a0<\/jats:italic>= 0.003). H<jats:sub>4<\/jats:sub>R agonist at nanomolar levels led to a rapid internalization of H<jats:sub>4<\/jats:sub>Rs, whereas high histamine concentration and interferon\u2010<jats:italic>\u03b3<\/jats:italic> decreased <jats:styled-content style=\"fixed-case\">HRH<\/jats:styled-content><jats:sub>4<\/jats:sub>\u2010gene transcripts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Healthy oral epithelial cells are equipped with H<jats:sub>4<\/jats:sub>R, which displays a uniform staining pattern in a <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>\u2010independent fashion. In contrast, in <jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content>, increased numbers of activated <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s associate with increasing loss of epithelial H<jats:sub>4<\/jats:sub>R. Cell culture experiments suggest a rapid H<jats:sub>4<\/jats:sub>R stimulation\u2010dependent receptor internalization and a slow cytokine\u2010driven decrease in H<jats:sub>4<\/jats:sub>R synthesis. H<jats:sub>4<\/jats:sub>R may be involved in the maintenance of healthy oral mucosa. In <jats:styled-content style=\"fixed-case\">OLP<\/jats:styled-content>, this maintenance might be impaired by <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> degranulation and inflammatory cytokines.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.12290","type":"journal-article","created":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T12:33:34Z","timestamp":1410352414000},"page":"378-385","source":"Crossref","is-referenced-by-count":20,"title":["Histamine H<sub>4<\/sub> receptor in oral lichen planus"],"prefix":"10.1111","volume":"21","author":[{"given":"A","family":"Salem","sequence":"first","affiliation":[{"name":"Department of Medicine University of Helsinki and Helsinki University Central Hospital Helsinki Finland"},{"name":"Department of Oral Pathology University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Al\u2010Samadi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Helsinki and Helsinki University Central Hospital Helsinki Finland"},{"name":"Department of Oral Pathology University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"Stegajev","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Helsinki and Helsinki University Central Hospital Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Stark","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmazeutische und Medizinische Chemie Heinrich\u2010Heine\u2010Universit\u00e4t D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"H\u00e4yrinen\u2010Immonen","sequence":"additional","affiliation":[{"name":"City of Helsinki Health Care Centre Helsinki 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