MiR-146a in Immunity and Disease.
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ABSTRACT:
SUBMITTER: Rusca N
PROVIDER: S-EPMC3200075 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Publications
MiR-146a in Immunity and Disease.
Rusca Nicole N Monticelli Silvia S
Molecular biology international 20110407
MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is ...[more]
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Project description: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) E? by COPD fibroblasts contributes to reduced repair function.The present study determined if fibroblasts from subjects with COPD overproduce PGE? after stimulation with the inflammatory cytokines IL-1? and tumor necrosis factor-?, and further defined the mechanism for overproduction.Fibroblasts were isolated from parenchymal tissue obtained from smokers with and without COPD undergoing lung surgery. PGE?, cyclooxygenases (COX), and miR-146a in these cells were evaluated by in vitro studies.After stimulation with inflammatory cytokines, COPD fibroblasts produced 2.7-fold more PGE? compared with controls with similar smoking history. The increase in PGE? 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 PGE? production and miR-146a expression in cultured fibroblasts correlated with clinical severity assessed by expiratory airflow and diffusion capacity.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.
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Project description:ObjectiveThe study aimed to explore the correlations of long non-coding RNA MALAT1 (lncRNA MALAT1) and its targets microRNA (miR)-125b, miR-133, miR-146a, and miR-203 with acute exacerbation risk, inflammation, and disease severity of chronic obstructive pulmonary disease (COPD).MethodsPlasma samples were obtained from 120 acute exacerbation COPD (AECOPD) patients, 120 stable COPD patients, and 120 healthy controls (HCs). RT-qPCR was conducted to detect lncRNA MALAT1 expression and its target miRNAs, and ELISA was performed to detect the inflammatory cytokines.ResultsLncRNA MALAT1 was highest in AECOPD patients followed by stable COPD patients and then HCs, which distinguished AECOPD patients from HCs (AUC: 0.969, 95% CI: 0.951-0.987) and stable COPD patients (AUC: 0.846, 95% CI: 0.798-0.894). Furthermore, lncRNA MALAT1 positively correlated with GOLD stage in both AECOPD and stable COPD patients. Regarding inflammatory cytokines, lncRNA MALAT1 positively correlated with tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-17, and IL-23 in both AECOPD and stable COPD patients. Besides, lncRNA MALAT1 negatively correlated with miR-125b, miR-146a, and miR-203 in AECOPD patients and reversely correlated with miR-125b and miR-146a in stable COPD patients. Notably, miR-125b, miR-133, miR-146a, and miR-203 were the lowest in AECOPD patients, followed by stable COPD patients, and then HCs; miR-125b, miR-133, miR-146a, and miR-203 negatively correlated with inflammation and GOLD stage in AECOPD and stable COPD patients.ConclusionLncRNA MALAT1 exhibits clinical implications in acute exacerbation risk prediction and management of COPD via the inner-correlation with its targets miR-125b, miR-146a, and miR-203.
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