Dataset Information
Reduced miR-146a increases prostaglandin E₂in chronic obstructive pulmonary disease fibroblasts.
Ontology highlight
ABSTRACT: Rationale
Persistent inflammation plays a major role in chronic obstructive pulmonary disease (COPD) pathogenesis, but its mechanisms are incompletely defined. Overproduction of the inflammatory mediator prostaglandin (PG) E₂ by COPD fibroblasts contributes to reduced repair function.Objectives
The present study determined if fibroblasts from subjects with COPD overproduce PGE₂ after stimulation with the inflammatory cytokines IL-1β and tumor necrosis factor-α, and further defined the mechanism for overproduction.Methods
Fibroblasts were isolated from parenchymal tissue obtained from smokers with and without COPD undergoing lung surgery. PGE₂, cyclooxygenases (COX), and miR-146a in these cells were evaluated by in vitro studies.Measurements and main results
After stimulation with inflammatory cytokines, COPD fibroblasts produced 2.7-fold more PGE₂ compared with controls with similar smoking history. The increase in PGE₂ depended on induction of COX-2, which increased to a greater degree in fibroblasts from subjects with COPD. Cytokines also induced microRNA miR-146a expression in both fibroblasts, but significantly less in COPD fibroblasts. miR-146a caused degradation of COX-2 mRNA; reduced expression prolonged COX-2 mRNA half-life in fibroblasts from subjects with COPD. Cytokine-stimulated PGE₂ production and miR-146a expression in cultured fibroblasts correlated with clinical severity assessed by expiratory airflow and diffusion capacity.Conclusions
miR-146a seems to play a pathogenetic role in the abnormal inflammatory response in COPD. Increased half-life of inflammatory mRNAs is a mechanism of abnormal inflammation in this disease.
SUBMITTER: Sato T
PROVIDER: S-EPMC2970844 | biostudies-literature | 2010 Oct
REPOSITORIES: biostudies-literature
Publications
Reduced miR-146a increases prostaglandin E₂in chronic obstructive pulmonary disease fibroblasts.
American journal of respiratory and critical care medicine 20100603 8
<h4>Rationale</h4>Persistent inflammation plays a major role in chronic obstructive pulmonary disease (COPD) pathogenesis, but its mechanisms are incompletely defined. Overproduction of the inflammatory mediator prostaglandin (PG) E₂ by COPD fibroblasts contributes to reduced repair function.<h4>Objectives</h4>The present study determined if fibroblasts from subjects with COPD overproduce PGE₂ after stimulation with the inflammatory cytokines IL-1β and tumor necrosis factor-α, and further define ...[more]
