Functional characterization of histamine receptor subtypes in a human bronchial epithelial cell line

Abstract

Abstract. Histamine is a well-known mediator eliciting a broad range of responses in different cell types. Four different subtypes of G protein-coupled histamine receptors (H 1 -H 4 ) have been cloned and pharmacologically characterized. However, involvement of the different histamine receptor subtypes in immunomodulatory functions of bronchial epithelium has only been investigated marginally. The expression and function of histamine receptor subtypes on the human bronchial epithelial cell line BEAS-2B was analyzed by PCR, intracellular Ca ++ -measurements and ELISA. We show mRNA expression of the histamine receptor subtypes H 1 , H 2 , and H 3 , but not H 4 in the human bronchial epithelial cell line BEAS-2B. Using intracellular Ca++ -measurements, we demonstrated functional expression of the H 1 and H 3 receptors. To characterize the biological properties of histamine in airway epithelial biology, we also investigated its effects on cytokine secretion by BEAS-2B cells. Thereby, we were able to show up-regulation of the proinflammatory mediators IL-6 and CXCL8/ IL-8 via activation of the H 1 , H 2 and H 3 receptor subtypes. The Th1 cytokines CXCL9/MIG and CXCL10/IP-10 and the chemokine CCL5/RANTES were regulated in a distinct manner: Whereas histamine inhibited the IFN-Á/TNF-·-induced secretion of MIG via the histamine receptor subtypes H 1 , H 2 , and H 3 , the histamine-induced suppression of RANTES was due to activation of the H 2 and H 3 receptors, while reduction of cytokine-triggered IP-10 secretion was mediated only by triggering the H 2 receptor. In summary our data provide evidence that histamine released during allergic lung diseases exerts regulatory influence on airway epithelial cells.

Histamine receptor expression in human renal tubules: a comparative pharmacological evaluation

“…It has been largely demonstrated that H 3 R is mostly expressed in the central and, to a lesser extent, in the peripheral nervous system. Only a small number of experimental observations have showed its presence on non-neuronal cell types such as rodent fundic mucosa endocrine cells [26], cholangiocytes [37], pancreatic β-cells [38], and in the human bronchial epithelial cell line BEAS-2B [39]. Therefore, our data add a new non-neuronal localization of the H 3 R, contributing to the hypothesis that the H 3 R could also mediate nonneuronal histamine effects.…”

Histamine H4 receptors in normal conjunctiva and in vernal keratoconjunctivitis

“…In a previous study in human dermal fibroblast cultures, H 4 R expression was unaffected by histamine stimulation (33). Expression of the H 1 R, H 2 R, and H 3 R, but not H 4 R was demonstrated in the human bronchial epithelial cell line (34). All these data suggest that the H 4 R is probably not critical in the regulatory effects of histamine on fibroblast and epithelial cell activation in allergic inflammation.…”

Potentiation of NF‐κB‐dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells

“…Previous studies in several different cell types have demonstrated NF‐κB activation and release of cytokines elicited by histamine acting via the H 1 receptor subtype (Bruysters et al , 2004; Wu et al , 2004; Matsubara et al , 2005; Jin et al , 2006; Muller et al , 2006). However, whereas inflammation is complex and involves multiple mediators, including histamine and pro‐inflammatory cytokines, most investigations have examined the effects of histamine acting alone.…”