Premium
Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus
Author(s) -
Salem A.,
Rozov S.,
AlSamadi A.,
Stegajev V.,
Listyarifah D.,
Kouri V.P.,
Han X.,
Nordström D.,
Hagström J.,
Eklund K.K.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14995
Subject(s) - histamine , histidine decarboxylase , histamine h4 receptor , histamine n methyltransferase , histamine receptor , diamine oxidase , histamine h1 receptor , autocrine signalling , chemistry , histamine h2 receptor , endocrinology , medicine , microbiology and biotechnology , biology , receptor , biochemistry , enzyme , histidine , antagonist
Summary Background Recent reports have indicated that nonimmune cells can produce low concentrations of histamine. This observation, together with the discovery of the high‐affinity histamine H 4 receptor (H 4 R), has added additional layers of complexity to our understanding of histamine signalling. Human oral keratinocytes ( HOK s) possess a uniform H 4 R pattern, which is deranged in oral lichen planus ( OLP ). Objectives To investigate histamine metabolism and transport in HOK s of healthy controls and patients with OLP . Methods Tissue sections and cultured primary HOK s were studied using immunostaining, quantitative real‐time polymerase chain reaction and confocal microscopy. Histamine levels were analysed using high‐performance liquid chromatography. Results l ‐histidine decarboxylase ( HDC ) and organic cation transporter ( OCT )3 were increased in mRNA and protein levels in patients with OLP compared with controls. In contrast, histamine N‐methyltransferase ( HNMT ) immunoreactivity was decreased in OLP . OCT 1/ OCT 2 and diamine oxidase were not detectable in either tissue sections or in HOK s. Immunolocalization of HDC and OCT 3 in HOK s revealed moderate‐to‐high expression within cytoplasm and cell boundaries. Stimulation with lipopolysaccharide ( LPS ) or interferon‐γ upregulated HDC ‐gene transcript in HOK s, whereas this was downregulated with high histamine concentration and tumour necrosis factor‐α. LPS induced a dose‐dependent release of low histamine in HOK s, while high histamine concentration downregulated epithelial adhesion proteins. Conclusions HOK s are histamine‐producing cells. They release histamine via OCT 3 channels in concentrations too low to activate the classical low‐affinity H 1 R and H 2 R, but high enough to stimulate the high‐affinity H 4 R in autocrine and paracrine modes. The substantially deranged histamine metabolism and transport in OLP could, in part, contribute to the disease pathogenesis.