Therapeutic targets for inflammation-mediated airway remodeling in chronic lung disease.

Abstract:

INTRODUCTION:Acute exacerbations of chronic lung disease account for substantial morbidity and health costs. Repeated inflammatory episodes and attendant bronchoconstriction cause structural remodeling of the airway. Remodeling is a multicellular response to mucosal injury that results in epithelial cell-state changes, enhanced extracellular deposition, and expansion of pro-fibrotic myofibroblast populations. Areas covered: This manuscript overviews mechanistic studies identifying key sentinel cell populations in the airway and how pattern recognition signaling induces maladaptive mucosal changes and airway remodeling. Studies elucidating how NFκB couples with an atypical histone acetyltransferase, bromodomain-containing protein 4 (BRD4) that reprograms mucosal fibrogenic responses, are described. The approaches to development and characterization of selective inhibitors of epigenetic reprogramming on innate inflammation and structural remodeling in preclinical models are detailed. Expert commentary: Bronchiolar cells derived from Scgb1a1-expressing progenitors function as major sentinel cells of the airway, responsible for initiating antiviral and aeroallergen responses. In these sentinel cells, activation of innate inflammation is coupled to neutrophilic recruitment, mesenchymal transition and myofibroblast expansion. Therapeutics targeting the NFkB-BRD4 may be efficacious in reducing pathological effects of acute exacerbations in chronic lung disease.

journal_name

Expert Rev Respir Med

authors

Brasier AR

doi

10.1080/17476348.2018.1526677

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

931-939

issue

11

eissn

1747-6348

issn

1747-6356

journal_volume

12

pub_type

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