MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.

ABSTRACT:

Background

Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis. The objective of this work was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in COPD in vitro and in vivo models.

Methods

MUC1-CT expression was measured by real time PCR, western blot, immunohistochemistry and immunofluorescence. The inflammatory mediators IL-8, MMP9, GM-CSF and MIP3? were measured by ELISA. The effect of MUC1 on inflammation and corticosteroid anti-inflammatory effects was measured using cell siRNA in vitro and Muc1-KO in vivo animal models.

Results

MUC1-CT expression was downregulated in lung tissue, bronchial epithelial cells and lung neutrophils from smokers (n?=?11) and COPD (n?=?11) patients compared with healthy subjects (n?=?10). MUC1 was correlated with FEV1% (??=?0.7479; p?ConclusionsThese results confirm a role for MUC1-CT mediating corticosteroid efficacy in COPD.

SUBMITTER: Milara J 

PROVIDER: S-EPMC6247701 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature