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Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.

Kinney SR, Carlson L, Ser-Dolansky J, Thompson C, Shah S, Gambrah A, Xing W, Schneider SS, Mathias CB - PLoS ONE (2015)

Bottom Line: In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation.Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs.In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119, United States of America.

ABSTRACT
IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

No MeSH data available.


Related in: MedlinePlus

Treatment of allergic mice with curcumin inhibits the activation of NF-κB.(A) Mice were fed with OVA and curcumin and sacrificed as depicted in Fig 1C. Immunohistochemistry on jejunal sections was performed as described in Materials and Methods. Phospho-relA staining (brown) in jejunal tissue is shown. Phospho-relA-positive mast cells as assessed by morphologic analysis are depicted by red arrows. (B) BMMCs were cultured with or without DNP-IgE and 30 μM curcumin in DMSO and activated in the presence of antigen 24 hours later. 12 hours later, protein was extracted from whole cell lysates and Western blot was performed. Data are representative of three experiments. (C) Quantification of the Western Blot data from B is shown.
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pone.0132467.g009: Treatment of allergic mice with curcumin inhibits the activation of NF-κB.(A) Mice were fed with OVA and curcumin and sacrificed as depicted in Fig 1C. Immunohistochemistry on jejunal sections was performed as described in Materials and Methods. Phospho-relA staining (brown) in jejunal tissue is shown. Phospho-relA-positive mast cells as assessed by morphologic analysis are depicted by red arrows. (B) BMMCs were cultured with or without DNP-IgE and 30 μM curcumin in DMSO and activated in the presence of antigen 24 hours later. 12 hours later, protein was extracted from whole cell lysates and Western blot was performed. Data are representative of three experiments. (C) Quantification of the Western Blot data from B is shown.

Mentions: A number of studies indicate that curcumin is a potent non-specific inhibitor of the transcription factor NF-κB [40–42], which is involved in the activation of both T and mast cells. To determine whether curcumin inhibits NF-κB activation in this model, we assessed the activation of NF-κB in the intestinal tissues of allergic mice (Fig 9A). The p65 (RelA) sub-unit of NF-κB plays a crucial role in the activation of NF-κB and its phosphorylation at Ser276 (phospho-relA staining) can be assessed by immunohistochemistry as previously described [33]. While the intestinal tissue of saline-sensitized and OVA-challenged control mice did not exhibit significant phospho-relA staining, the number of phospho-relA+ cells (including mast cells as assessed by morphologic analysis) in the intestines of OVA-sensitized and challenged mice was dramatically increased, suggesting that the induction of allergic responses is accompanied by NF-κB activation. In contrast, the intestines of OVA-exposed, curcumin-treated mice appeared to be similar to those of saline-treated controls suggesting that curcumin inhibits the activation of NF-κB. These data, therefore, suggest that the inhibitory effects of curcumin on mast cells in our model may be conferred by blocking the activation of NF-κB.


Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.

Kinney SR, Carlson L, Ser-Dolansky J, Thompson C, Shah S, Gambrah A, Xing W, Schneider SS, Mathias CB - PLoS ONE (2015)

Treatment of allergic mice with curcumin inhibits the activation of NF-κB.(A) Mice were fed with OVA and curcumin and sacrificed as depicted in Fig 1C. Immunohistochemistry on jejunal sections was performed as described in Materials and Methods. Phospho-relA staining (brown) in jejunal tissue is shown. Phospho-relA-positive mast cells as assessed by morphologic analysis are depicted by red arrows. (B) BMMCs were cultured with or without DNP-IgE and 30 μM curcumin in DMSO and activated in the presence of antigen 24 hours later. 12 hours later, protein was extracted from whole cell lysates and Western blot was performed. Data are representative of three experiments. (C) Quantification of the Western Blot data from B is shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493063&req=5

pone.0132467.g009: Treatment of allergic mice with curcumin inhibits the activation of NF-κB.(A) Mice were fed with OVA and curcumin and sacrificed as depicted in Fig 1C. Immunohistochemistry on jejunal sections was performed as described in Materials and Methods. Phospho-relA staining (brown) in jejunal tissue is shown. Phospho-relA-positive mast cells as assessed by morphologic analysis are depicted by red arrows. (B) BMMCs were cultured with or without DNP-IgE and 30 μM curcumin in DMSO and activated in the presence of antigen 24 hours later. 12 hours later, protein was extracted from whole cell lysates and Western blot was performed. Data are representative of three experiments. (C) Quantification of the Western Blot data from B is shown.
Mentions: A number of studies indicate that curcumin is a potent non-specific inhibitor of the transcription factor NF-κB [40–42], which is involved in the activation of both T and mast cells. To determine whether curcumin inhibits NF-κB activation in this model, we assessed the activation of NF-κB in the intestinal tissues of allergic mice (Fig 9A). The p65 (RelA) sub-unit of NF-κB plays a crucial role in the activation of NF-κB and its phosphorylation at Ser276 (phospho-relA staining) can be assessed by immunohistochemistry as previously described [33]. While the intestinal tissue of saline-sensitized and OVA-challenged control mice did not exhibit significant phospho-relA staining, the number of phospho-relA+ cells (including mast cells as assessed by morphologic analysis) in the intestines of OVA-sensitized and challenged mice was dramatically increased, suggesting that the induction of allergic responses is accompanied by NF-κB activation. In contrast, the intestines of OVA-exposed, curcumin-treated mice appeared to be similar to those of saline-treated controls suggesting that curcumin inhibits the activation of NF-κB. These data, therefore, suggest that the inhibitory effects of curcumin on mast cells in our model may be conferred by blocking the activation of NF-κB.

Bottom Line: In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation.Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs.In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Administrative Sciences, College of Pharmacy, Western New England University, Springfield, MA 01119, United States of America.

ABSTRACT
IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

No MeSH data available.


Related in: MedlinePlus