Objective: Long non-coding RNAs (lncRNAs) are novel, important molecules regulating cellular gene expression. Human monocytes are important inflammatory cells which contribute to arteriosclerosis development and inflammatory processes. We studied monocytic lncRNA expression to identify potential novel anti-inflammatory mechanisms. 

Results: RNA sequencing of human monocytes and the monocytic cell line THP-1 revealed several highly expressed lncRNAs, among them MANTIS. Interestingly, MANTIS expression massively decreased during monocyte differentiation pointing to a specific function of the lncRNA in monocytes. Given that monocytes sense danger associated molecules like TLR-ligands, we speculated that MANTIS might be required for the inflammatory response of monocytes. To study this aspect, THP-1 cells were treated with TLR ligands Lipopolysaccharide-LPS, Flagellin, Lipoteichoic acid with and without CRISPR/Cas9-mediated deletion of MANTIS. Importantly, TLR-mediated pro-inflammatory gene expression was masively attenuated after knockout of MANTIS. Luciferase reportergen assays demonstrated that deletion of MANTIS supresses NF-kB, but not AP-1 and STAT1 promoter activity. MANTIS, however, did not affect NF-kB nuclear recruitment. In contrast, TLR-mediated recruitment of the NF-kB subunit p65 to the transcriptional start site of inflammatory genes was significantly reduced after MANTIS knockout as demonstrated by chromatin immunoprecipitation (ChIP).  

Conclusion: The lncRNA Mantis is involved in NF-kB signaling and therefore impacts expression of inflammation-related genes. MANTIS is a novel attractive target for anti-inflammatory therapy.