Repeated Pre-treatment With Antihistamines Causes Transcriptional Up-regulations of Histamine H1 Receptor and Interleukin-4 Genes in Toluene-2,4-diisocyanate–Sensitized Rats

Mizuguchi, Hiroyuki; Hatano, Masaya; Matsushita, Chiyo; Umehara, Hayato; Kuroda, Wakana; Kitamura, Y.; Takeda, Noriaki; Fukui, Hirokazu

doi:10.1254/jphs.08222fp

Cited by 45 publications

(34 citation statements)

References 32 publications

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“…This hypothesis is supported by recent findings that prophylactic treatment with H 1 antihistamines suppressed the TDI-induced up-regulation of H1R and IL-4 mRNAs in TDI-sensitized rats (34). To explore this possibility, we applied rrIL-4 or histamine directly to FIGURE 2.…”

Section: Effect Of Il-4 or Histamine On Nasal Mucosal H1r Or Il-4 Mrnmentioning

confidence: 55%

“…These findings suggest the existence of multiple, H1R-mediated and non-H1R-mediated pathways for H1R mRNA up-regulation. Recently, we reported that prophylactic treatment with H 1 antihistamines suppressed TDI-induced up-regulation of both H1R and IL-4 mRNAs in TDI-sensitized rats (34). Direct administration of IL-4 into the nasal cavity of non-TDI-treated normal rats up-regulated the expression of H1R mRNA (Fig.…”

Section: Discussionmentioning

confidence: 84%

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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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Section: Effect Of Il-4 or Histamine On Nasal Mucosal H1r Or Il-4 Mrnmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 84%

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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“…We think IL-4 may be a candidate responsible for H1R mRNA up-regulation. We have reported that prophylactic treatment with H 1 -antihistamines suppressed TDI-induced up-regulations of both H1R and IL-4 mRNAs in TDI-sensitized rats (71). Direct administration of IL-4 into the nasal cavity of non-TDI-treated normal rats up-regulated the expression of H1R mRNA (unpublished result).…”

Section: Discussionmentioning

confidence: 81%

Kujin Suppresses Histamine Signaling at the Transcriptional Level in Toluene 2,4-Diisocyanate–Sensitized Rats

et al. 2009

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Abstract. Kujin, the dried root of Sophorae flavescensis, has been used in Chinese folklore medicine against allergy. Evaluation of its anti-allergic potential as well as its mechanism of action has rarely been established. We investigated the effect of Kujin on toluene-2,4-diisocyanate (TDI)-induced allergic behavior and related histamine signaling including mRNA levels of histamine H 1 receptor (H1R) and histidine decarboxylase (HDC), H1R and HDC activities, and histamine content in rat nasal mucosa. We also investigated the effect of Kujin on the mRNA levels of helper T cell type 2 (Th2)-cytokine genes closely related to histamine signaling. TDI provocation caused acute allergic symptoms accompanied with up-regulations of H1R and HDC mRNAs and increases in HDC activity, histamine content, and [ 3 H]mepyramine binding activity in the nasal mucosa, all of which were significantly suppressed by pretreatment with Kujin for 3 weeks. Kujin also suppressed the TDI-induced IL-4 and IL-5 mRNA elevations. These data suggest that oral administration of Kujin showed anti-allergic activity through suppression of histamine signaling by the inhibition of TDI-induced H1R and HDC mRNA elevations followed by decrease in H1R, HDC protein level, and histamine content in the nasal mucosa of TDI-sensitized rats. Suppression of Th2-cytokine signaling by Kujin also suggests that it could affect the histamine-cytokine network.

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“…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)(12)(13)(14)(15)(16). These findings suggest that the H1R gene is an allergy-sensitive gene, i.e.…”

mentioning

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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Repeated Pre-treatment With Antihistamines Causes Transcriptional Up-regulations of Histamine H1 Receptor and Interleukin-4 Genes in Toluene-2,4-diisocyanate–Sensitized Rats

Cited by 45 publications

References 32 publications

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

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

Kujin Suppresses Histamine Signaling at the Transcriptional Level in Toluene 2,4-Diisocyanate–Sensitized Rats

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

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