Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor

Abstract

H4R is highly expressed on keratinocytes from patients with atopic dermatitis, and its stimulation induces keratinocyte proliferation. This might represent a mechanism that contributes to the epidermal hyperplasia observed in patients with atopic dermatitis.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…In this case, treatment with H 4 receptor antagonists were anti-inflammatory and led to a reduction in the number of mast cells and eosinophils in the affected skin (Cowden et al, 2010b). In addition to effects on eosinophils, the H 4 receptor also mediates keratinocyte proliferation, which may explain some of the effects seen in the model (Glatzer et al, 2013). Finally, the combination of H 1 receptor and H 4 receptor antagonists was more effective than either alone in two models of contact dermatitis (Matsushita et al, 2012;Ohsawa and Hirasawa, 2012).…”

“…Certain polymorphisms of the human H 4 receptor gene that should result in an increased expression or signaling of the receptor were associated with atopic dermatitis (Yu et al, 2010b). Along this line, keratinocytes derived from patients with atopic dermatitis expressed higher levels of the H 4 receptor mRNA compared with keratinocytes from patients without skin disease or psoriasis (Glatzer et al, 2013). In asthma, there appeared to be a link between three single nucleotide polymorphisms in the H 4 receptor gene and infectioninduced asthma (Simon et al, 2012).…”

“…Mice deficient in H 2 receptor function display cognitive deficits, an impairment in hippocampal long-term potentiation (Dai et al, 2007), and abnormalities in nociception (Mobarakeh et al, 2005(Mobarakeh et al, , 2006, gastric, and immune functions (Jutel et al, 2001;Teuscher et al, 2004;Schneider et al, 2014a). The suppression of immune responses via the H 2 receptor was not only shown in H 2 receptor-deficient mice but also in human antigen presenting cells, where H 2 receptor stimulation resulted in the downregulation of numerous cytokines (Gutzmer et al, 2005;Glatzer et al, 2013).…”

“…Expression coupled with function defined by pharmacological methods has been shown on mast cells; eosinophils; neutrophils; dendritic cells; Langerhans cells; natural killer cells; monocytes; T cells, including gdT cells, T helper 1, 2, and 17 cells; keratinocytes; inflammatory dendritic epidermal cells; and fibroblasts (Gantner et al, 2002;Hofstra et al, 2003;Ling et al, 2004;Lippert et al, 2004;Gutzmer et al, 2005Gutzmer et al, , 2009Sander et al, 2006;Damaj et al, 2007;Dijkstra et al, 2007Dijkstra et al, , 2008Godot et al, 2007;Bäumer et al, 2008;Ikawa et al, 2008;Yamaura et al, 2009;Gschwandtner et al, 2010Gschwandtner et al, , 2011Gschwandtner et al, , 2012Gschwandtner et al, , 2013Truta-Feles et al, 2010;Mommert et al, 2012;Glatzer et al, 2013;Mirzahosseini et al, 2013;Cowden et al, 2014;Czerner et al, 2014;Dib et al, 2014;Jemima et al, 2014). In addition, expression data, but as to date no functional data, have been reported in epithelial cells and basophils (Hofstra et al, 2003;Sander et al, 2006).…”

Histamine H4 Receptor in Allergic Dermatitis

“…Keratinocytes on human epidermal tissue express HH4R [37] . Outer root sheath keratinocytes of AD increase the expression of HH4R compared with keratinocytes of healthy donors [38] .…”