An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness.

ABSTRACT: It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A₄ hydrolase (LTA₄H) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B₄ (LTB₄) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB₄ signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTA₄H exacerbated AHR, despite the absence of LTB₄ This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling

SUBMITTER: Patel DF 

PROVIDER: S-EPMC6342449 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature