Gram-negative (G-) bacteria frequently induce an overwhelming inflammatory response in hosts. Despite years of research, the regulation of the inflammatory response after G- bacterial infection remains unclear, thus impeding the development of novel therapeutic/diagnostic strategies. Mammalian genomes encode thousands of long non-coding RNAs (lncRNAs). LncRNAs are extensively expressed in various immune cells including the monocytes, and macrophages. The lncRNAs have been reported to be involved in diverse biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but as yet very less research has been carried out to explore how they alter cell differentiation/function during host- pathogens interactions. We found that Lincenc1 is strikingly induced in the lungs obtained from the mice infected with G- bacteria or after exposure to LPS, an abundant glycolipid of the outer membrane of G- bacteria. Furthermore, our in vitro data suggest that Lincenc1 is induced in macrophages but not in other cells, such as the epithelial cells and neutrophils. Functionally, Lincenc1 promotes the classical activation of macrophages and the secretion of inflammatory cytokines. Here we propose that lncRNA Lincenc1 promotes G- bacterial/LPS induced lung inflammation via activating alveolar macrophages. To test this hypothesis, we propose the following two specific aims:
Specific Aim I : To investigate the role of Lincenc1 in macrophage activation in vitro.
Specific Aim 2 : To investigate the role of Lincenc1 in lung inflammation in vivo. Successful completion of the proposed aims will uncover the role of Lincenc1 in G- bacterial infections. This study potentially will help to identify novel mechanisms and/or therapeutic strategies for lung inflammation and injury.
Severe lung inflammatory responses and respiratory failure often occur in the setting of G- bacterial-pneumonia. We hypothesize that lncRNA Lincenc1 promotes G-bacteria/LPS induced lung inflammation via activating alveolar macrophages.
|Zhang, Duo; Lee, Heedoo; Wang, Xiaoyun et al. (2018) Exosome-Mediated Small RNA Delivery: A Novel Therapeutic Approach for Inflammatory Lung Responses. Mol Ther 26:2119-2130|