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Sphingosine kinase-1-dependent and -independent inhibitory effects of zanthoxyli fructus to attenuate the activation of mucosal mast cells and ameliorate food allergies in mice.

Wang X, Kageyama-Yahara N, Hayashi S, Yamamoto T, Kadowaki M - Evid Based Complement Alternat Med (2012)

Bottom Line: As a result, both antigen-induced and calcium ionophore-induced degranulation was significantly inhibited by Zanthoxyli Fructus water extract (ZF) in mucosal-type murine bone marrow-derived mast cells (mBMMCs).Furthermore, ZF inhibited allergic symptoms in an ovalbumin-caused murine FA model and decreased the number of infiltrating mucosal mast cells and the enhanced mRNA expression levels of IL-4 and Sphk1 in the FA mice colons.These results indicate that ZF suppresses mucosal mast cell activities mainly through Sphk1-dependent mechanism, and ZF is utilized for the development of a novel, potent anti-FA agent.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

ABSTRACT
Food allergy (FA) is relatively a common disease in infants, but effective drug therapies are not yet available. Notably, mucosal mast cells, but not connective-tissue mast cells, play important roles in food allergic reactions via the release of inflammatory mediators. Therefore, we screened medicinal herb extracts for in vitro and in vivo antiallergic activity through inhibiting mucosal mast cell activation. As a result, both antigen-induced and calcium ionophore-induced degranulation was significantly inhibited by Zanthoxyli Fructus water extract (ZF) in mucosal-type murine bone marrow-derived mast cells (mBMMCs). ZF suppressed the antigen-induced [Ca(2+)](i) elevation and the antigen-enhanced mRNA expression of TNF-α, IL-4, and IL-13. The transcriptome and real-time PCR analyses revealed that ZF greatly decreased the antigen-enhanced expression level of sphingosine kinase 1 (Sphk1), which plays a key role in the FcεRI-mediated immune responses in mast cells. Furthermore, ZF inhibited allergic symptoms in an ovalbumin-caused murine FA model and decreased the number of infiltrating mucosal mast cells and the enhanced mRNA expression levels of IL-4 and Sphk1 in the FA mice colons. These results indicate that ZF suppresses mucosal mast cell activities mainly through Sphk1-dependent mechanism, and ZF is utilized for the development of a novel, potent anti-FA agent.

No MeSH data available.


Related in: MedlinePlus

The effect of ZF and DMS on the development of FA in vivo. (a) The induction of allergic diarrhea was compared between the vehicle- and ZF-treated groups. ZF was orally administered during the induction of allergic diarrhea by OVA oral challenge as described in the Materials and Methods section (n = 8). (b) DMS (1 mg/kg) suppressed the incidence of allergic diarrhea (n = 5–8). (c) The proximal colons of the vehicle, ZF (320 mg/kg), and DMS (1 mg/kg) treated mice after oral challenge with OVA were stained with anti-mMCP1 antibody. The scale bar represents 200 μm. (d) The expression levels of IL-4 and sphk1 in the proximal colons were measured using real-time PCR. The results are expressed as the relative ratio to the proximal colons of the vehicle-treated FA mice. The data are expressed as the mean ± SD (n = 5). *P < 0.05 compared with the vehicle.
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fig6: The effect of ZF and DMS on the development of FA in vivo. (a) The induction of allergic diarrhea was compared between the vehicle- and ZF-treated groups. ZF was orally administered during the induction of allergic diarrhea by OVA oral challenge as described in the Materials and Methods section (n = 8). (b) DMS (1 mg/kg) suppressed the incidence of allergic diarrhea (n = 5–8). (c) The proximal colons of the vehicle, ZF (320 mg/kg), and DMS (1 mg/kg) treated mice after oral challenge with OVA were stained with anti-mMCP1 antibody. The scale bar represents 200 μm. (d) The expression levels of IL-4 and sphk1 in the proximal colons were measured using real-time PCR. The results are expressed as the relative ratio to the proximal colons of the vehicle-treated FA mice. The data are expressed as the mean ± SD (n = 5). *P < 0.05 compared with the vehicle.

Mentions: In OVA-challenged mice (FA mice), allergic diarrhea began to occur after the third oral OVA challenge (Figure 6(a)). The administration of ZF (320 mg/kg) significantly reduced the incidence of OVA-induced diarrhea, and the incidence of diarrhea was decreased to approximately 40% after the sixth OVA challenge. As shown in Figure 6(b), the administration of DMS (1 mg/kg) likewise significantly reduced the incidence of diarrhea. Furthermore, the number of mucosal mast cells that were observed by immunohistochemistry with mMCP-1 antibody dramatically increased in the proximal colons of FA mice compared with the number in normal mice, which is consistent with our previous paper [6]. ZF and DMS dramatically decreased the number of infiltrating mucosal mast cells in the proximal colons of the FA mice (Figure 6(c)). In addition, as shown in Figure 6(d), ZF repressed the mRNA expression of IL-4 and Sphk1 in the proximal colons of the FA mice.


Sphingosine kinase-1-dependent and -independent inhibitory effects of zanthoxyli fructus to attenuate the activation of mucosal mast cells and ameliorate food allergies in mice.

Wang X, Kageyama-Yahara N, Hayashi S, Yamamoto T, Kadowaki M - Evid Based Complement Alternat Med (2012)

The effect of ZF and DMS on the development of FA in vivo. (a) The induction of allergic diarrhea was compared between the vehicle- and ZF-treated groups. ZF was orally administered during the induction of allergic diarrhea by OVA oral challenge as described in the Materials and Methods section (n = 8). (b) DMS (1 mg/kg) suppressed the incidence of allergic diarrhea (n = 5–8). (c) The proximal colons of the vehicle, ZF (320 mg/kg), and DMS (1 mg/kg) treated mice after oral challenge with OVA were stained with anti-mMCP1 antibody. The scale bar represents 200 μm. (d) The expression levels of IL-4 and sphk1 in the proximal colons were measured using real-time PCR. The results are expressed as the relative ratio to the proximal colons of the vehicle-treated FA mice. The data are expressed as the mean ± SD (n = 5). *P < 0.05 compared with the vehicle.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375181&req=5

fig6: The effect of ZF and DMS on the development of FA in vivo. (a) The induction of allergic diarrhea was compared between the vehicle- and ZF-treated groups. ZF was orally administered during the induction of allergic diarrhea by OVA oral challenge as described in the Materials and Methods section (n = 8). (b) DMS (1 mg/kg) suppressed the incidence of allergic diarrhea (n = 5–8). (c) The proximal colons of the vehicle, ZF (320 mg/kg), and DMS (1 mg/kg) treated mice after oral challenge with OVA were stained with anti-mMCP1 antibody. The scale bar represents 200 μm. (d) The expression levels of IL-4 and sphk1 in the proximal colons were measured using real-time PCR. The results are expressed as the relative ratio to the proximal colons of the vehicle-treated FA mice. The data are expressed as the mean ± SD (n = 5). *P < 0.05 compared with the vehicle.
Mentions: In OVA-challenged mice (FA mice), allergic diarrhea began to occur after the third oral OVA challenge (Figure 6(a)). The administration of ZF (320 mg/kg) significantly reduced the incidence of OVA-induced diarrhea, and the incidence of diarrhea was decreased to approximately 40% after the sixth OVA challenge. As shown in Figure 6(b), the administration of DMS (1 mg/kg) likewise significantly reduced the incidence of diarrhea. Furthermore, the number of mucosal mast cells that were observed by immunohistochemistry with mMCP-1 antibody dramatically increased in the proximal colons of FA mice compared with the number in normal mice, which is consistent with our previous paper [6]. ZF and DMS dramatically decreased the number of infiltrating mucosal mast cells in the proximal colons of the FA mice (Figure 6(c)). In addition, as shown in Figure 6(d), ZF repressed the mRNA expression of IL-4 and Sphk1 in the proximal colons of the FA mice.

Bottom Line: As a result, both antigen-induced and calcium ionophore-induced degranulation was significantly inhibited by Zanthoxyli Fructus water extract (ZF) in mucosal-type murine bone marrow-derived mast cells (mBMMCs).Furthermore, ZF inhibited allergic symptoms in an ovalbumin-caused murine FA model and decreased the number of infiltrating mucosal mast cells and the enhanced mRNA expression levels of IL-4 and Sphk1 in the FA mice colons.These results indicate that ZF suppresses mucosal mast cell activities mainly through Sphk1-dependent mechanism, and ZF is utilized for the development of a novel, potent anti-FA agent.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

ABSTRACT
Food allergy (FA) is relatively a common disease in infants, but effective drug therapies are not yet available. Notably, mucosal mast cells, but not connective-tissue mast cells, play important roles in food allergic reactions via the release of inflammatory mediators. Therefore, we screened medicinal herb extracts for in vitro and in vivo antiallergic activity through inhibiting mucosal mast cell activation. As a result, both antigen-induced and calcium ionophore-induced degranulation was significantly inhibited by Zanthoxyli Fructus water extract (ZF) in mucosal-type murine bone marrow-derived mast cells (mBMMCs). ZF suppressed the antigen-induced [Ca(2+)](i) elevation and the antigen-enhanced mRNA expression of TNF-α, IL-4, and IL-13. The transcriptome and real-time PCR analyses revealed that ZF greatly decreased the antigen-enhanced expression level of sphingosine kinase 1 (Sphk1), which plays a key role in the FcεRI-mediated immune responses in mast cells. Furthermore, ZF inhibited allergic symptoms in an ovalbumin-caused murine FA model and decreased the number of infiltrating mucosal mast cells and the enhanced mRNA expression levels of IL-4 and Sphk1 in the FA mice colons. These results indicate that ZF suppresses mucosal mast cell activities mainly through Sphk1-dependent mechanism, and ZF is utilized for the development of a novel, potent anti-FA agent.

No MeSH data available.


Related in: MedlinePlus