Dataset Information

Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.

ABSTRACT:

Background

Oral exposure to food allergens may be limited in infancy, and the initial site of antigen exposure likely plays an important role in food allergy induction.

Objective

To examine the impact of different routes of exposure by using milk allergens, with and without adjuvant, on sensitization.

Methods

C3H/HeJ mice were repeatedly exposed to the milk allergen ?-lactalbumin (ALA), with or without cholera toxin (CT). Sensitization routes used were intragastric, cutaneous, intranasal, and sublingual. Anaphylaxis severity was assessed by symptoms and body temperature in response to oral challenge. Antigen-specific serum antibodies were measured by ELISA. The mechanism of adjuvant activity of cutaneous CT was also determined.

Results

Sensitization to ALA as measured by allergen-specific IgE occurred by all routes of sensitization and was maximal in response to cutaneous exposure. Sensitization was dependent on CT and did not occur to antigen alone by any route. Mucosal, but not cutaneous, exposure resulted in a robust allergen-specific IgA response. Anaphylaxis occurred in all sensitized groups when orally challenged with ALA. Topical CT induced migration of langerin(neg) dermal dendritic cells to the lymph node, resulting in enhanced proliferation and T(H)2 cytokine production from responder T cells.

Conclusions

Sensitization can occur via all physiologic routes when adjuvant is present. The skin is a potent and likely important physiologic route of sensitization whereby adjuvant induces an efflux of antigen-bearing dermal dendritic cells to the lymph node that generate a proallergic T(H)2 response.

SUBMITTER: Dunkin D

PROVIDER: S-EPMC3197891 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Publications

Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.

Dunkin David D Berin M Cecilia MC Mayer Lloyd L

The Journal of allergy and clinical immunology 20110718 6

<h4>Background</h4>Oral exposure to food allergens may be limited in infancy, and the initial site of antigen exposure likely plays an important role in food allergy induction.<h4>Objective</h4>To examine the impact of different routes of exposure by using milk allergens, with and without adjuvant, on sensitization.<h4>Methods</h4>C3H/HeJ mice were repeatedly exposed to the milk allergen α-lactalbumin (ALA), with or without cholera toxin (CT). Sensitization routes used were intragastric, cutaneo ...[more]

PMID: 21762973

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Project description:Background:Doxorubicin (DOX) is one of the most effective anti-neoplastic drugs although its clinical use is limited by the severe cardiotoxicity. Apoptosis and defective autophagy are believed to contribute to DOX-induced cardiotoxicity. Here we explored the effect of curcumin (Cur) on DOX-induced cardiac injury and the mechanism involved with a focus on oxidative stress, autophagy and pyroptosis. Methods:Kunming mice were challenged with DOX (3 mg·kg-1, i.p. every other day) with cohorts of mice receiving Cur at 50, 100, 200 and 400 mg·kg-1 via gavage daily. Serum levels of cardiac enzymes, such as aspartate amino transferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and heart homogenate oxidative stress markers, such as superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Echocardiographic and cardiac contraction were examined. Apoptosis, pyroptosis, autophagy and Akt/mTOR-signalling proteins were detected using western blot or electron microscopy. Cardiac contractile properties were assessed including peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-PS, and time-to-90% relengthening (TR90). Superoxide levels were evaluated using DHE staining. GFP-LC3 was conducted to measure autophagosomes. Results:Our study showed that Cur protected against cardiotoxicity manifested by a significant decrease in serum myocardial enzymes and improvement of anti-oxidative capacity. Cur inhibited autophagy and offered overt benefit for cardiomyocyte survive against DOX-induced toxicity. Cur attenuated DOX-induced cardiomyocyte pyroptosis as evidenced by NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and interleukin-18 levels. DOX impaired cardiac function (reduced fractional shortening, ejection fraction, increased plasma cTnI level and TR90, decreased PS and ± dL/dt), the effects of which were overtly reconciled by 100 mg·kg-1 but not 50 mg·kg-1 Cur. H9c2 cells exposure to DOX displayed increased intracellular reactive oxygen species (ROS) and autophagy, the effects of which were nullified by Cur. Autophagy activator rapamycin cancelled off Cur-induced protective effects. Conclusions:Our finding suggested that Cur rescued against DOX-induced cardiac injury probably through regulation of autophagy and pyroptosis in a mTOR-dependent manner.

Dataset Information

Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.

Background

Objective

Methods

Results

Conclusions

Publications

Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.

Similar Datasets

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