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Protease Inhibitor Reduces Airway Response and Underlying Inflammation in Cockroach Allergen-Induced Murine Model

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Abstract

Protease(s) enhances airway inflammation and allergic cascade. In the present study, effect of a serine protease inhibitor was evaluated in mouse model of airway disease. Mice were sensitized with cockroach extract (CE) or Per a 10 and treated with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) 1 h before or after challenge to measure airway response. Mice were euthanized to collect bronchoalveolar lavage fluid (BALF), blood, and lung to evaluate inflammation. AEBSF treatment significantly reduced the AHR in allergen-challenged mice in dose-dependent manner (p ≤ 0.01). IgE (p ≤ 0.05) and Th2 cytokines (p ≤ 0.05) were significantly reduced in treated mice. AEBSF treatment lowered total cell (p ≤ 0.05), eosinophil (p ≤ 0.05), and neutrophil (p ≤ 0.05) in BALF and lung tissue. Oxidative stress parameters were impaired on treatment in allergen-challenged mice (p ≤ 0.05). AEBSF had therapeutic effect in allergen-induced airway resistance and underling inflammation and had potential for combination or as add-on therapy for respiratory diseases.

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Abbreviations

AEBSF :

4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride

BAL :

Bronchoalveolar lavage

BALF :

Bronchoalveolar lavage fluid

CE :

Cockroach extract

DCFH-DA :

2′,7′-Dichlorfluorescein-diacetate

MCh :

Methacholine

MFI :

Mean fluorescence intensity

PEEP :

Positive end expiratory pressure

ROS :

Reactive oxygen species

RT :

Room temperature

SEM :

Standard error mean

TMB :

3,3′,5,5′-Tetramethylbenzidine

OPD :

o-Phenylenediamin

PAS :

Periodic acid–Schiff

HRP :

Horseradish peroxidase

NADPH :

Nicotinamide adeninedinucleotide phosphate ELISAEnzyme-linked immunosorbent assay

Ns :

Not significant

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Acknowledgments

One of the authors (Sanjay Saw) is a “Junior Research Fellow” from University Grant Commission, Delhi. The authors are thankful to CSIR-network project for financial support to this study.

Conflict of Interest

The authors have no competing interests.

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Authors and Affiliations

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

    Sanjay Saw & Naveen Arora

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

    Sanjay Saw

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Correspondence to Naveen Arora.

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Saw, S., Arora, N. Protease Inhibitor Reduces Airway Response and Underlying Inflammation in Cockroach Allergen-Induced Murine Model. Inflammation 38, 672–682 (2015). https://doi.org/10.1007/s10753-014-9976-0

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  • DOI: https://doi.org/10.1007/s10753-014-9976-0

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