Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3.

ABSTRACT

OBJECTIVE: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. METHODS: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. RESULTS: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1ß. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. CONCLUSIONS: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.