Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthmaReport as inadecuate




Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma - Download this document for free, or read online. Document in PDF available to download.

Respiratory Research

, 12:19

First Online: 01 December 2011Received: 20 August 2010Accepted: 03 February 2011

Abstract

BackgroundArginase overexpression contributes to airways hyperresponsiveness AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR.

MethodsTo investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin OVA and challenged with nebulized PBS OVA-PBS or OVA OVA-OVA for three consecutive days sub-acute model or 12 weeks chronic model, which exhibit inflammatory cell influx and remodeling-AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone CAP+O3, or HEPA-filtered air FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization.

ResultsCompared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA-OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models.

ConclusionsThis study demonstrates that arginase is upregulated following environmental exposures in murine models of asthma, and contributes to the pollution-induced exacerbation of airways responsiveness. Thus arginase may be a therapeutic target to protect susceptible populations against the adverse health effects of air pollution, such as fine particles and ozone, which are two of the major contributors to smog.

AbbreviationsAHRairways hyperresponsiveness

BALbronchoalveolar lavage

BECS-boronoethyl-L- cysteine

CAPconcentrated ambient particles

EC50half-maximal effective concentration

FAfiltered air

Gperipheral tissue damping

NOSnitric oxide synthase

O3ozone

OVAovalbumin

PBSphosphate buffered saline

Rtotal resistance of the respiratory system

RNresistance of the central airways.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-19 contains supplementary material, which is available to authorized users.

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Author: Michelle L North - Hajera Amatullah - Nivedita Khanna - Bruce Urch - Hartmut Grasemann - Frances Silverman - Jeremy A Sco

Source: https://link.springer.com/







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