Abstract
Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs). LncRNAs are extensively expressed in various immune cells. The lncRNAs have been reported to be involved in diverse biological processes, including the regulation of gene expression, dosage compensation, and genomic imprinting. However, very little research has been conducted to explore how they alter innate immune responses during host-pathogen interactions. In this study, we found that a lncRNA, named long noncoding RNA, embryonic stem cells expressed 1 (Lncenc1), was strikingly increased in mouse lungs after gram-negative (G-) bacterial infection or exposure to lipopolysaccharides (LPS). Interestingly, our data indicated that Lncenc1 was upregulated in macrophages but not in primary epithelial cells (PECs) or polymorphonuclear leukocytes (PMN). The upregulation was also observed in human THP-1 and U937 macrophages. Besides, Lncenc1 was highly induced during ATP-induced inflammasome activation. Functionally, Lncenc1 showed proinflammatory effects in macrophages as demonstrated by increased expressions of cytokine and chemokines, as well as enhanced NF-κB promoter activity. Overexpression of Lncenc1 promoted the releases of IL-1β and IL-18, and Caspase-1 activity in macrophages, suggesting a role in inflammasome activation. Consistently, knockdown of Lncenc1 inhibited inflammasome activation in LPS-treated macrophages. Moreover, knockdown of Lncenc1 using antisense oligo (ASO)-loaded exosomes (EXO) attenuated LPS-induced lung inflammation in mice. Similarly, Lncenc1 deficiency protects mice from bacteria-induced lung injury and inflammasome activation. Taken together, our work identified Lncenc1 as a modulator of inflammasome activation in macrophages during bacterial infection. Our study suggested that Lncenc1 could serve as a therapeutic target for lung inflammation and injury.
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More From: American Journal of Physiology-Lung Cellular and Molecular Physiology
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