Chronic inflammatory airway diseases, characterized by airway inflammation and airway remodelling, are increasing as a cause of morbidity and mortality for all age groups and races across the world. The underlying molecular mechanisms involved in chronic inflammatory airway diseases have not been fully explored. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have recently attracted much attention for their roles in the regulation of a variety of biological processes. A number of studies have confirmed that both lncRNAs and miRNAs can regulate the initiation and progression of chronic airway diseases by targeting mRNAs and regulating different cellular processes, such as proliferation, apoptosis, inflammation, migration, and epithelial–mesenchymal transition (EMT). Recently, accumulative evidence has shown that the novel regulatory mechanism underlying the interaction among lncRNAs, miRNAs and messenger RNAs (mRNAs) plays a critical role in the pathophysiological processes of chronic inflammatory airway diseases. In this review, we comprehensively summarized the regulatory roles of the lncRNA–miRNA–mRNA network in different cell types and their potential roles as biomarkers, indicators of comorbidities or therapeutic targets for chronic inflammatory airway diseases, particularly chronic obstructive pulmonary disease (COPD) and asthma.

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Acute lung injury (ALI) is an acute and progressive pulmonary inflammatory disease that is difficult to cure and has a poor prognosis. Macrophages, which have various phenotypes and diverse functions, play an essential role in the pathogenesis of ALI. Grape seed proanthocyanidin (GSP) has received much attention over several decades, and many biological activities such as anti-apoptotic, antioxidant, and anti-inflammatory have been identified. This study aimed to determine the effect of GSP on lipopolysaccharide (LPS)-induced ALI. In this study, we established an ALI mouse model by tracheal instillation of LPS, and by pre-injection of GSP into mice to examine the effect of GSP on the ALI mouse model. Using H&E staining, flow cytometry, and ELISA, we found that GSP attenuated LPS-induced lung pathological changes and decreased inflammatory cytokine expression in ALI mice. In addition, GSP reduced the recruitment of monocyte-derived macrophages to the lung and significantly promoted the polarization of primary mouse lung macrophages from M1 to M2a induced by LPS. In vitro, GSP also decreased the expression levels of inflammatory cytokines such as TNF-α, IL-6, IL-1β, and M1 macrophage marker iNOS induced by LPS in MH-S cells, while increasing the expression levels of M2a macrophage marker CD206. Bioinformatics analysis identified TREM2 and the PI3K/Akt pathway as candidate targets and signaling pathways that regulate M1/M2a macrophage polarization in ALI, respectively. Furthermore, GSP activated PI3K/Akt and increased TREM2 expression in vivo and in vitro. Meanwhile, GSP's impact on M2a polarization and inflammation suppression was attenuated by the PI3K inhibitor LY294002 or siRNA knockdown TREM2. In addition, GSP-enhanced PI3K/Akt activity was prevented by TREM2 siRNA. In conclusion, this study demonstrated that GSP could ameliorate LPS-induced ALI by modulating macrophage polarization from M1 to M2a via the TREM2/PI3K/Akt pathway.