Long non‐coding RNAs regulate NF‐κB activation, inflammation, and glucose metabolism

Abstract

Inflammation plays a central role in immune response and the inflammatory response is closely linked with metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF‐kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in regulation of glucose metabolism in immune cells during inflammation. Our study demonstrate that lncRNA HOTAIR regulates the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake into macrophages. SiRNA‐mediated knockdown of HOTAIR suppressed the LPS‐induced expression of Glut1 and glucose update in macrophages suggesting key roles of HOTAIR in LPS‐induced Glut1 expression and glucose metabolism. HOTAIR induces NF‐kB activation which in turn increases Glut1 expression and glucose metabolism in response to LPS. Beyond HOTAIR, we also discovered several novel lncRNAs (termed as LinfRNA: Long‐noncoding inflammation associated RNA) which are closely associated with inflammation and metabolism. Overall, our study demonstrated that HOTAIR and LinfRNAs play key roles in NF‐kB activation and inflammation and regulate metabolic programming in immune cells potentially to meet the energy needs at the priming of immune response to pathogenic infection or other stressors.Support or Funding InformationNational Institute of Health grant # 1R15 ES019129‐01