Histamine H₄ receptor in oral lichen planus

Abstract

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.

Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus

“…Thus, drugs targeting its effects have been used in clinics since the 1940s. MCs represent a primary source of histamine and they are highly increased in OLP . However, classical antihistamines have not been effective in the treatment of OLP and, consequently, clinical trials targeting the low‐affinity H 1 R and H 2 R in OLP and other autoimmune diseases have been abandoned …”

“…Supernatants were collected and stored for further functional analysis. Degranulated MCs can produce micromolar concentrations of histamine and we have previously shown that H 4 R in HOKs is downregulated after 24 h exposure to 50 μmol L −1 histamine . HOKs were therefore incubated with 50 μmol L −1 histamine (Sigma‐Aldrich, St Louis, MO, U.S.A.), 100 ng mL −1 recombinant‐human interferon (rhIFN)‐γ or 100 ng mL −1 recombinant‐human tumour necrosis factor‐α (rhTNF‐α) both from R&D Systems Inc. (Minneapolis, MN, U.S.A.).…”

“…Oral lichen planus (OLP) is a chronic inflammatory disease that is characterized by a dense T‐cell infiltrate below an apoptotic epithelial basal cell layer and degenerated basement membrane (BM) . Recently, we showed that human oral keratinocytes (HOKs) possess a uniform H 4 R pattern and that the expression of H 4 R was significantly decreased in patients with OLP compared with controls . We have studied the capacity of HOKs to metabolize and transport histamine in healthy controls and in patients with OLP.…”

Epithelial Cell Apoptosis in Recurrent Aphthous Ulcers

“…Oral keratinocytes cell line was used in several immunologic studies. In some of these studies, keratinocyte cell line was compared with the primary keratinocytes in terms of IL-8 production and histamine 4 receptor expression after activation of the cells with different stimuli; both cells respond to the stimulations similarly (Uehara et al 2005;Uehara et al 2007;Salem et al 2015).…”

Histamine reduces boron neutron capture therapy‐induced mucositis in an oral precancer model

“…Although JNJ7777120 was initially considered as a standard H4R antagonist, recent evidence suggests that JNJ7777120 may also act as agonist to human H4R (Martinel Lamas et al , ). It has been reported that healthy oral epithelial cells are equipped with H4R, displaying a uniform staining pattern (Salem et al , ). In the digestive system, H4R expression has been evidenced in different areas and in a variety of cell types, including immune, inflammatory, neural endocrine, and epithelial cells (Medina et al , ).…”