Air pollution exposure leads to various inflammatory diseases in the human respiratory system. Chronic rhinosinusitis is an inflammatory disease caused by viruses, bacteria, or air pollutants. However, the underlying molecular mechanisms through which air particulate matter (PM) causes inflammation and disease remain unclear. In this article, we report that the induction of exosomal microRNAs (miRNAs) from human nasal epithelial cells upon airborne PM exposure promotes proinflammatory M1 macrophage polarization via downregulated RORa expression. Exposure of human nasal epithelial cells to PM results in inflammation-related miRNA expression, and more miRNA is secreted through exosomes delivered to macrophages. Among these, miRNA-19a and miRNA-614 directly bind to the 39-untranslated region of RORa mRNA and downregulate RORa expression, which leads to inflammation due to inflammatory cytokine upregulation and induces macrophages to a proinflammatory M1-like state. Finally, we showed enhanced expression of miRNA-19a and miRNA-614 but reduced RORa expression in a chronic rhinosinusitis patient tissue compared with the normal. Altogether, our results suggest that PM-induced exosomal miRNAs might play a crucial role in the proinflammatory mucosal microenvironment and macrophage polarization through the regulation of RORa expression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.