lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma 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 PBMCs of children with asthma 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 real-time quantitative PCR, Western blot, RNase protection assay, and chromatin immunoprecipitation 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 children with asthma, 502 of which were upregulated and 217 were downregulated. An lncRNA of unknown function, lnc-BAZ2B, was dominantly expressed in monocytes and significantly upregulated in children with asthma. lnc-BAZ2B promotes M2 macrophage activation by enhancing BAZ2B expression and exacerbated lung inflammation in an 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 children with asthma. Baz2b knockdown could alleviate asthma severity in a CRE-induced asthma model.

Conclusion: lnc-BAZ2B promotes M2 macrophage activation and inflammation in children with asthma and may serve as a potential therapeutic and diagnostic target in children with asthma.

Keywords: Asthma; BAZ2B; lncRNA; macrophage activation.