Long noncoding RNA MEG3-4 regulates IL-1β during pulmonary bacterial infection by repressing microRNA-138

Long noncoding RNAs (lncRNAs) modulate various biological processes; however, their function in host immunity response against infection is largely unknown. Here, we identify an intergenic lncRNA MEG3 (linc-MEG3) as a tissue specific regulator for pulmonary immunity during Gram-negative bacterial infection. Among the 10 transcripts of linc-MEG3, transcripts 1 and 4 are main regulators as being discovered the most downregulated in mouse lungs after bacterial infection. Overexpression of linc-MEG3-4 in mice led to intensified inflammatory response, severe lung injury, systemic dissemination and ultimately increased mortality. Alveolar epithelial cells and alveolar macrophages (AM) were major cell populations that are targeted by linc-MEG3-4. Due to its 3′ sequences complementary to microRNA-138 (miR-138), linc-MEG3-4 competitively binds miR-138 and thereby freeing its target IL-1β mRNA to intensify inflammatory responses. Our results characterize linc-MEG3 as a novel pulmonary inflammatory regulator of bacterial infection through a miR-138/IL-1β/NF-κB axis.