Suppression of Histamine Signaling by Probiotic Lac-B: a Possible Mechanism of Its Anti-allergic Effect

Dev, Shrabanti; Mizuguchi, Hiroyuki; Das, Asish Kumar; Matsushita, Chiyo; Maeyama, Kazutaka; Umehara, Hayato; Ohtoshi, Takayuki; Kojima, Jun; Nishida, Kensei; Takahashi, Kyoko; Fukui, Hirokazu

doi:10.1254/jphs.08028fp

Cited by 40 publications

(42 citation statements)

References 33 publications

(19 reference statements)

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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: 93%

“…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: 93%

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: 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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“…Both cytokines are TH2-derived, with IL-4 acting on Bcells to induce class-switching and on mast cells to induce degranulation and further cytokine production and IL-5 inducing eosinophil degranulation. Specific strains found to inhibit IL-4 and IL-5 production include L. casei (Schiffer et al, 2009), L. rhamnosus (Ghadimi et al, 2008), B. longum (Takahashi et al, 2006) and B. infantis (Dev et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

The Immunomodulatory Effects of Probiotic Bacteria on Peripheral Blood Mononuclear Cells (Pbmcs) of Allergic Patients

Sheikh¹,

Shalaby²,

Hafez³

et al. 2014

American Journal of Immunology

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Allergic diseases represent major health burden. An allergic reaction is characterized by a disrupted Thelper 1⁄T-helper 2 balance toward a preferential allergen specifically induced TH2 cytokine profile, causing allergic inflammation Probiotic bacteria have various benificial effects in many pathologic situation. Studies have shown that the bacteria present in the intestinal micro flora play a role in the TH1/TH2 balance and its modulation can promote the control of infectious and immune processes. Testing the effects of probiotic bacteria on TH1/TH2 cytokine production by peripheral blood mononuclear cells of allergic patients and control subjects. This study included 24 patients allergic to date pollen and 16 healthy control subjects. PBMC of both groups were separated and cultured for 72 h with date pollen allergen (home-made) in the presence or absence of Lactobacillus rhamnosus ATCC 7469 (Living and dead) and Cphycocyanin (extracted from Spirulina platensis). The cell culture supernatants were collected to measure Interlukin 4 and Interferon gamma by quantitative ELISA. Incubation of PBMCs of allergic patients with living Lactobacillus rhamnosus ATCC 7469 showed marked reduction in IL4 production (median IL4 concentarion = 3.9 pg.) compared to PBMCs callenged with pollen alone (mediam IL4 conentration = 52.6 pg). When PBMC were incubated with living Lactobacillus rhamnosus in absence of allergen significant increase in and IFNγ (median concentration = 42.75 pg.) was obtained, compared to PBMC challenged with allergen alone (median = 22.8 pg). When PBMCs incubated with heat killed Lactobacillus rhamnosus either in presence or absence of the offending allergen, marked reduction in IL4 production was obtained (median = 10.6, 3.6 pg respectively) compared to PBMC incubated with allergen alone (median = 52.6 pg). When PBMCs incubated with dead Lactobacillus rhamnosus, marked increase in IFNγ production was obtained (median = 49 pg) when compared to IFNγ production by PBMC challenged with allergen (median 22.8 pg). PBMCs challenged with PC in the presence or absence of allergen showed marked decrease of IL4 production (median = 19.8, 17 pg respectively) when compared to PBMC incubated with the offending allergen alone (median = 52.6 pg). PBMCs incubated with PC showed significant increase of and IFNγ production (median= 319.6 pg) when compared to PBMC incubated with the offending allergen alone (median = 22.8 pg). Conclusion Lactobacillus rhamnosus ATCC 7469 and C-phycocyanin (extracted from Spirulina platensis) inversed the TH1: TH2 polarization in allergic patients and could be a promissing line of treatmen.

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Suppression of Histamine Signaling by Probiotic Lac-B: a Possible Mechanism of Its Anti-allergic Effect

Cited by 40 publications

References 33 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

The Immunomodulatory Effects of Probiotic Bacteria on Peripheral Blood Mononuclear Cells (Pbmcs) of Allergic Patients

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