Novel long non-coding RNAs associated with inflammation and macrophage activation in human

Abstract

Inflammation plays a central role in immune response and macrophage activation. Emerging studies demonstrate that along with proteins and genomic factors, noncoding RNA are potentially involved in regulation of immune response and inflammation. Our recent study demonstrated that lncRNA HOTAIR plays key roles in cytokine expression and inflammation in macrophages. The primary goal of this study is to discover novel lncRNAs that are crucial players in inflammation, macrophage activation, and immune response in humans. Towards this, we have stimulated THP1-derived macrophages (THP1-MΦ) with lipopolysaccharides (LPS) and performed the whole transcriptome RNA-seq analysis. Based on this analysis, we discovered that along with well-known marker for inflammation (such as cytokines), a series of long noncoding RNAs (lncRNAs) expression were highly induced upon LPS-stimulation of macrophages, suggesting their potential roles in inflammation and macrophage activation. We termed these family of lncRNAs as Long-noncoding Inflammation Associated RNA (LinfRNA). Dose and time dependent analysis demonstrated that many human LinfRNA (hLinfRNAs) expressions follow similar patterns as cytokine expressions. Inhibition of NF-κB suppressed the expression of most hLinfRNAs suggesting their potential regulation via NF-κB activation during inflammation and macrophage activation. Antisense-mediated knockdown of hLinfRNA1 suppressed the LPS-induced expression of cytokines and pro-inflammatory genes such as IL6, IL1β, and TNFα expression, suggesting potential functionality of the hLinfRNAs in cytokine regulation and inflammation. Overall, we discovered a series of novel hLinfRNAs that are potential regulators of inflammation and macrophage activation and may be linked to inflammatory and metabolic diseases.