Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes

Early reports indicate that long non-coding RNAs (IncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs (eRNAs), 40 canonical IncRNAs, 65 antisense IncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown of nuclear-localized, NF-kappa B-regulated, eRNAs (IL1 beta-eRNA) and RBT (IL1 beta-RBT46) surrounding the IL1 beta locus, attenuates LPS-induced messenger RNA transcription and release of the proinflammatory mediators, IL1 beta and CXCL8. We predict that IncRNAs can be important regulators of the human innate immune response.