Lnc-BAZ2B promotes M2 macrophage activation and inflammation in asthmatic children through stabilizing BAZ2B pre-mRNA

Abstract Background Dysregulation of long noncoding RNAs (lncRNAs) is associated with a variety of human diseases; however, whether they have a role in childhood asthma is unknown. Objective We sought to determine the differential expression profiles of lncRNAs in peripheral blood mononuclear cell (PBMCs) of asthmatic children and the mechanisms underlying the effects of lncRNAs on the pathogenesis of asthma. Methods The differential expression profiles of lncRNAs were analyzed by transcriptome microarray. The effects and mechanisms by which lncRNAs influence macrophage activation were detected by RT-qPCR, western blot, RNase protection assay, and ChIP assay. The roles played by lncRNAs in asthma were tested in a cockroach allergen extract (CRE)-induced mouse model. Results We identified 719 lncRNAs that were differentially expressed in PBMCs of asthmatic children, 502 of which were upregulated and 217 downregulated. A lncRNA of unknown function, lnc-BAZ2B, was dominantly expressed in monocytes and significantly upregulated in asthmatic children. Lnc-BAZ2B promotes M2 macrophages activation by enhancing BAZ2B expression and exacerbated lung inflammation in a M2 macrophage-associated CRE-induced asthma model. Mechanistically, lnc-BAZ2B promoted the expression of its cis target gene BAZ2B by stabilizing its pre-mRNA. BAZ2B, a reader of H3K14ac modification, enhanced the transcription of IRF4 and promoted M2 macrophage activation. Lnc-BAZ2B expression was correlated with that of BAZ2B in PBMCs from asthmatic children. Baz2b knockdown could alleviate asthma severity in CRE induced asthma model. Conclusion Lnc-BAZ2B promotes M2 macrophage activation and inflammation in asthmatic children and may serve as potential therapeutic and diagnostic targets in asthmatic children.