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Proteolytically Inactive Per a 10 Allergen of Periplaneta americana Modulates Th2 Response and Enhances IL-10 in Mouse Model

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Abstract

Background

Purified allergens with reduced IgE reactivity are required to improve the safety and efficacy of allergen-specific immunotherapy (IT).

Objective

The present study investigates the efficacy of purified cockroach allergen immunotherapy with proteolytically active and inactive Per a 10 in allergic mouse model.

Methods

Balb/c mice were sensitized intraperitoneally with cockroach extract (CE) and purified allergen Per a 10 in separate groups. Mice were treated subcutaneously with phosphate-buffered saline (PBS), CE, active and inactive Per a 10 and challenged intranasally. Antigen specific IgE, IgG1 and IgG2a in serum and cytokines IL-4, IL-13, IFN-γ, IL-10, TGF-β in bronchoalveolar lavage (BAL) fluid and spleen culture supernatant (CS) were estimated by enzyme-linked immunosorbent assay. Lung histology was analyzed by hematoxylin and eosin staining.

Results

IT with Per a 10 demonstrated significant reduction in IgE levels in serum, IL-4 levels in BAL fluid, CS, and eosinophilic infiltration in lungs than PBS-treated mice. This was associated with significantly increased IL-10 secretion in BAL fluid and CS. IT with Per a 10 effectively suppressed T-helper type 2 (Th2) response in mice sensitized with Per a 10 than CE group. Further, IT with inactive Per a 10 showed maximum reduction in systemic and airway inflammation and induced maximum IL-10 release in BAL fluid and CS than other antigens.

Conclusions

IT with Per a 10 effectively suppressed Th2 response and lung inflammation in Per a 10- or CE-sensitized mice. The beneficial effects of IT with inactive Per a 10 are more pronounced than active Per a 10.

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Abbreviations

SIT:

Specific Immunotherapy

CS:

Spleen culture supernatant

EDTA:

Ethylenediamine tetraceticacid

AEBSF:

Aminoethyl benzenesulfonyl fluoride hydrochloride

PMSF:

Phenylmethylsulfonyl fluoride

BAEE:

N-Benzoyl arginine ethyl ester hydrochloride

CE:

Whole body cockroach extract

w/v :

Weight/volume

SDS:

Sodium dodecyl sulfate

PBS:

Phosphate-buffered saline

ELISA:

Enzyme-linked immunosorbent assay

BAL:

Bronchoalveolar lavage

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Acknowledgment

One of the authors (Deepsikha) received financial assistance from Council of Scientific and Industrial Research, New Delhi, India.

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Authors and Affiliations

  1. Allergy and Immunology Section, Institute of Genomics and Integrative Biology (CSIR), Delhi University Campus, Room 509, Mall Road, Delhi, 110007, India

    Deepsikha Srivastava, Amit Kumar Mehta, Naveen Arora & Bhanu Pratap Singh

  2. Department of Biotechnology, University of Pune, Ganeskhind, Pune, India, 411007

    Deepsikha Srivastava & Amit Kumar Mehta

  3. Department of Pulmonary Medicine, V. P. Chest Institute, University of Delhi, Delhi, India, 110007

    Shailendra Nath Gaur

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  1. Deepsikha Srivastava
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  2. Amit Kumar Mehta
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Correspondence to Bhanu Pratap Singh.

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Srivastava, D., Mehta, A.K., Arora, N. et al. Proteolytically Inactive Per a 10 Allergen of Periplaneta americana Modulates Th2 Response and Enhances IL-10 in Mouse Model. J Clin Immunol 30, 426–434 (2010). https://doi.org/10.1007/s10875-009-9362-0

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