No abstract

Post-transcriptional regulation of gene expression by microRNAs has been implicated in the regulation of chronic physiological and pathological responses. In this report, we demonstrate that changes in the expression of microRNAs (miRNAs) can also regulate acute inflammatory responses in human lung alveolar epithelial cells. Thus, stimulation with interleukin (IL)-1β results in a rapid time- and concentration-dependent increase in miRNA-146a and, to a lesser extent, miRNA-146b expression although these increases were only observed at high IL-1β concentration. Examination of miRNA function by over-expression and inhibition showed that increased miRNA-146a expression negatively regulated the release of the pro-inflammatory chemokines, IL-8 and RANTES. Subsequent examination of the mechanism demonstrated that the action of miRNA-146a was mediated at the translational level and not through down-regulation of proteins involved in the IL-1β signalling pathway or chemokine transcription or secretion. Overall, these studies indicate that rapid increase in miRNA-146a expression provides a novel mechanism for negative regulation of severe inflammation during the innate immune response.

It is increasingly clear that long non-coding RNAs (lncRNAs) regulate a variety biological responses, and that they do so by a diverse range of mechanisms. In the field of immunology, recent publications have shown widespread changes in the expression of lncRNAs during the activation of the innate immune response and T cell development, differentiation, and activation. These lncRNAs control important aspects of immunity such as production of inflammatory mediators, differentiation, and cell migration through regulating protein-protein interactions or via their ability to basepair with RNA and DNA. We review the current understanding of the mechanism of action of these immune-related lncRNAs, discuss their impact on physiological and pathological processes, and highlight important areas of inquiry at the intersection between immunology and lncRNA biology.