Increased expression of p22phox mediates airway hyperresponsiveness in an experimental model of asthma

Abstract

AIM: Chronic airway diseases such as asthma are associated with increased production of reactive oxygen species (ROS) and oxidative stress. Endogenous NADPH oxidases are a major source of superoxide in lung, but their underlying role in asthma pathology is poorly understood. We sought to characterize the involvement of NADPH oxidase in allergic asthma by studying the role of CYBA (p22phox) in human asthma and murine house dust mite (HDM)-induced allergic airway inflammation.

RESULTS: Increased expression and localisation of p22-PHOX was observed in biopsies of asthmatic patients. HDM treated wild-type mice possessed elevated p22phox expression, corresponded with elevated superoxide production. p22phox knockout (KO) mice did not induce superoxide and were protected against HDM-induced goblet cell hyperplasia and mucus production and HDM-induced airway-hyperreactivity (AHR). IL-13 induced tracheal hyperreactivity and Signal transducer and activator of transcription (STAT)6 phosphorylation was attenuated in the absence of p22phox or catalase pretreatment.

INNOVATION: Our study identifies increased expression of p22phox in lungs of asthmatic patients and in experimental model. The induced AHR and mucus hypersecretion is result of an increased ROS from the p22phox dependent NADPH oxidase, which in turn activates STAT6 for the pathological feature of Asthma.

CONCLUSIONS: Together with the increased p22phox expression in lungs of asthmatic patients, these findings demonstrate a crucial role of p22phox dependent NADPH oxidase for the development of mucus hypersecretion and AHR in HDM-induced model of asthma. This suggests inhibition of functional NADPH oxidase by selective interference of p22phox might hold promising therapeutic strategy for the management of asthma.

More information

Identifiers

Catalogue record

Export record

ASCII CitationAtomBibTeXData Cite XMLDublin CoreDublin CoreEP3 XMLEndNoteHTML CitationHTML CitationHTML ListJSONMETSMODSMPEG-21 DIDLOpenURL ContextObjectOpenURL ContextObject in SpanRDF+N-TriplesRDF+N3RDF+XMLRIOXX2 XMLReferReference ManagerSimple Metadata

Altmetrics