Sho-seiryu-to Suppresses Histamine Signaling at the Transcriptional Level in TDI-Sensitized Nasal Allergy Model Rats

Das, Asish Kumar; Mizuguchi, Hiroyuki; Kodama, Madoka; Dev, Shrabanti; Umehara, Hayato; Kitamura, Yoshiaki; Matsushita, Chiyo; Takeda, Noriaki; Fukui, Hirokazu

doi:10.2332/allergolint.o-07-526

Cited by 31 publications

(24 citation statements)

References 43 publications

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“…Additionally, TDI-sensitized rats also display many of the characteristic features of AR in humans, including infiltration of eosinophils and mast cells (40), increase in the level of cytokines (8,(41)(42)(43), elevation of H1R mRNA and protein level (12), increase in the HDC mRNA level, HDC activity, and histamine content (13), even though histamine release was triggered by neuropeptide, but not IgE, in TDI-sensitized animals. Furthermore, the expression of IL-4 and IL-5 mRNAs was also up-regulated in the nasal mucosa of TDI-sensitized rats after provocation with TDI (16,17). Therefore, we consider that TDI-sensitized rats can be a model of AR.…”

Section: Discussionmentioning

confidence: 95%

“…Among them, IL-4 plays a central role in allergic inflammation: it is associated with the development of T lymphocytes, acts as a growth factor for Th2 cells, stimulates IgE synthesis, and is involved in mast cell activation (15). Previous reports that the expression of IL-4 and IL-5 mRNAs was up-regulated in nasal mucosa suggest the involvement of these cytokines in nasal hyperresponsiveness in TDI-sensitized rats (16,17).…”

Section: A Llergic Rhinitis (Ar)mentioning

confidence: 99%

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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: Discussionmentioning

confidence: 95%

Section: A Llergic Rhinitis (Ar)mentioning

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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“…The H1R expression level is highly correlated to the severity of allergic symptoms, and compounds that suppress H1R gene expression alleviate allergic symptoms (12)(13)(14)(15)(16). Therefore, drugs targeting the proteins that compose the signaling pathway involved in histamine-induced up-regulation of H1R gene expression could be good therapeutics for allergic diseases.…”

Section: Discussionmentioning

confidence: 99%

“…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: 91%

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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“…Furthermore, there are several in vivo reports concerning SST immunomoduratory action on allergic pathology, such as suppression of Th2 differentiation at the level ofsynapse between antigenpresenting cells and CD4+ T cells (7), inhibition of histamine signaling targeting its receptor expression and synthesizing enzyme (8), and augmentation of NGF induction accompanied by allergic pathology.…”

Section: Discussionmentioning

confidence: 99%

In vitro Action of Sho-Seiryu-to on Allergen-Exposed Mononuclear Cells

Tanaka

Inoue

Kitamura

et al. 2014

Int J Immunopathol Pharmacol

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Although Sho-seiryu-to (SST), used as a traditional herbal (Kampo) medicine mainly in China and Korea, is shown to have immunomodulating potential, such as an anti-allergic one, its underlying mechanism has not been completely clarified. To partially address the issue, we explored its effects on allergen-exposed mononuclear cells. Male balb/c mice were intraperitoneally administered ovalbumin (OVA: 20 Jlg) plus alum or vehicle twice (Day 0 and Day 14). At Day 21, mice were sacrificed and splenocytes (mononuclear cells) were isolated and cultured in the presence or absence of OVA with or without SST. Thereafter, helper T-related cytokines in the culture supernatants were evaluated by means of ELISA. Protein level of interferon-y was lower than 5.0 pglmL in the supernatants from OVAnon-exposed or -exposed mononuclear cells in the presence or absence of OVA stimulation. On the other hand, SST induced the cytokine from both types of mononuclear cells in the presence (P < 0.05) or absence of OVA stimulation as compared to corresponding control. By contrast, interleukin (IL)-4 level tended to be decreased by SST in OVA-non-exposed mononuclear cells as did IL-13 in both non-exposed and exposed mononuclear cells as compared to vehicle. In conclusion, immunoregulating efficacy by SST on allergy-prone subjects may include, at least in part, restoring helper T balance mainly through hyperproduction of IFN-y against mononuclear cells such as lymphocytes.The prevalence of allergic disorders has rapidly increased, especially in urban areas, over the past decades (l). Although it has not been directly correlated with a fatal outcome, the irritable symptoms reduce labor effectiveness and the quality of life of patients and the economic burden of this condition accounts for some rates (2, 3). Mechanistically, T helper 2 response and consequent Igfi-mediated pathobiology in mast cells/basophils could be largely involved in the development of allergic diseases, therefore, its treatment has generally focused on suppressing these cellular and molecular processes, which represent antihistamines, steroids, and thromboxane A2 and leukotriene receptor antagonists. However, long-term use of these drugs can evoke adverse health reactions such as weight gain and liver damage, as well as antihistamine-and steroid-related reactions; thus, alternative therapeutic approach strategy, possibly in combination with these previous treatments, is required to minimize these reactions.A herbal (Kampo) medicine, Sho-seiryu-to (SST),

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Sho-seiryu-to Suppresses Histamine Signaling at the Transcriptional Level in TDI-Sensitized Nasal Allergy Model Rats

Cited by 31 publications

References 43 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

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

In vitro Action of Sho-Seiryu-to on Allergen-Exposed Mononuclear Cells

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