Expression of Histamine Receptors in Nasal Epithelial Cells and Endothelial Cells – The Effects of Sex Hormones

Hamano, Nanako; Terada, Nobuhisa; Maesako, Ken-ichi; Ikeda, Tatehiko; Fukuda, Setsuya; Wakita, Jun; Yamashita, Tetsuji; Konno, Akiyoshi

doi:10.1159/000023904

Cited by 88 publications

(52 citation statements)

References 23 publications

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“…We also reported that the H1R mRNA level in TDI rats was significantly higher than that of control animals (13). These findings were in line with studies in which the expression of H1R mRNA was increased in epithelial and endothelial cells of nasal mucosa (14), in neural cells (15), and in the nasal scrapings from patients with nasal allergy (4). It has also been reported that H1R binding activity in the nasal mucosa is increased with the development of nasal allergy (16).…”

Section: Discussionsupporting

confidence: 90%

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

et al. 2007

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Abstract. Histamine is a major mediator in allergy acting mainly through the histamine H 1 receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H 2 receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced upregulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their longterm inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.

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Section: Discussionsupporting

confidence: 90%

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

et al. 2007

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“…This finding led to a working hypothesis of the existence of a detrimental circuit between histamine and H1R in which histamine-induced up-regulation of H1R gene expression results in an increase in the amount of H1R protein, and this makes the cells more sensitive to histamine and may actually exacerbate the allergic symptoms. It was reported that expression of H1R mRNA was increased in epithelial, endothelial, and neural cells on the nasal mucosa in the patients with occupational rhinitis (34,35). Up-regulation of H1R was also observed in patients with allergic rhinitis (6, 7).…”

Section: Discussionmentioning

confidence: 98%

Involvement of Protein Kinase Cδ/Extracellular Signal-regulated Kinase/Poly(ADP-ribose) Polymerase-1 (PARP-1) Signaling Pathway in Histamine-induced Up-regulation of Histamine H1 Receptor Gene Expression in HeLa Cells

Mizuguchi

Terao

Kitai

et al. 2011

Journal of Biological Chemistry

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The histamine H 1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12- Histamine is a major chemical mediator of allergic reactions, and its action is mainly mediated by the histamine H 1 receptor (H1R), 2 which is one of the four histamine receptor isoforms. H1R, which is a G protein-coupled receptor, is coupled to the G q protein. The stimulation of H1R activates inositol phospholipid hydrolysis and intracellular Ca 2ϩ mobilization. Typically, the activation of G protein-coupled receptors by their agonists induces down-regulation of the receptors. However, to date, a few reports have demonstrated up-regulation of G proteincoupled receptors by their agonists (1-4). Previously, we found that histamine stimulation up-regulated H1R at both the mRNA and protein level via activation of H1R in HeLa cells that express H1R endogenously (5). Up-regulation of H1R has been observed in patients with allergic rhinitis (6, 7). The strength of H1R signaling depends on the H1R expression level (8). Our recent studies have demonstrated that the level of H1R gene expression is strongly correlated with the severity of allergic symptoms in model rats and patients with pollinosis (9, 10), and compounds that suppress H1R gene up-regulation alleviate allergic symptoms (11-16). These findings suggest that the H1R gene is an allergy-sensitive gene, i.e. its expression level affects the severity of symptoms. Hence, understanding the molecular mechanism of H1R up-regulation may be useful for developing new anti-allergic drugs that target H1R gene expression. However, the mechanism of H1R up-regulation in response to histamine is unknown.Previously, we demonstrated that PKC-dependent signaling is involved in up-regulation of H1R gene expression in HeLa cells (5). PKC consists of at least 11 isoforms, and based on their structures and cofactor requirements, the PKC isoforms are divided into three subgroups; that is, conventional PKC (␣, ␤, and ␥), novel PKC (␦, ⑀, , and ), and atypical PKC ( and /) (17). It has been reported that PKC ␣, ␤, ␦, ⑀, and isoforms are expressed in HeLa cells (18 -20).Coupling of H1R signaling with PKC␣ has been reported in H1R-overexpressing CHO cells (21) and native human epidermal keratinocytes (22). In these cells, however, no up-regulation of H1R gene expression was observed. In addition, NF-B (23), the cAMP response element-binding protein (CREB) (24)), the nuclear factor of activated T-cell (25), and the serumresponsive element (26)

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“…Expression of H1R mRNA is reported to increase in epithelial, endothelial, and neural cells on the nasal mucosa in the patients with occupational rhinitis (46,47). H1R binding activity in the nasal mucosa is also reported to increase during development of nasal allergy (48).…”

Section: Discussionmentioning

confidence: 99%

Suplatast Tosilate Inhibits Histamine Signaling by Direct and Indirect Down-Regulation of Histamine H1 Receptor Gene Expression through Suppression of Histidine Decarboxylase and IL-4 Gene Transcriptions

Shahriar

Mizuguchi

Maeyama

et al. 2009

The Journal of Immunology

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Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as sneezing, congestion, and rhinorrhea. Histamine plays important roles in eliciting AR symptoms. Up-regulation of the histamine H1 receptor (H1R) and histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines are also involved in the pathogenesis of AR. We examined the effect of suplatast tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene-2,4-diisocyanate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R. Provocation with TDI increased nasal symptoms, HDC activity, the histamine content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs. Suplatast also suppressed HDC activity in the nasal mucosa and the histamine content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal cavity of normal rats up-regulated H1R mRNA, while intranasal application of histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA elevation. These results suggest that suplatast alleviates nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through the suppression of histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL-4 gene transcriptions, respectively.

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Expression of Histamine Receptors in Nasal Epithelial Cells and Endothelial Cells – The Effects of Sex Hormones

Cited by 88 publications

References 23 publications

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

Stimulation of Histamine H1 Receptor Up-Regulates Histamine H1 Receptor Itself Through Activation of Receptor Gene Transcription

Involvement of Protein Kinase Cδ/Extracellular Signal-regulated Kinase/Poly(ADP-ribose) Polymerase-1 (PARP-1) Signaling Pathway in Histamine-induced Up-regulation of Histamine H1 Receptor Gene Expression in HeLa Cells

Suplatast Tosilate Inhibits Histamine Signaling by Direct and Indirect Down-Regulation of Histamine H1 Receptor Gene Expression through Suppression of Histidine Decarboxylase and IL-4 Gene Transcriptions

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