The aim of this study is to identify the role of NRIR in LPS treated human CD14+ monocytes. RNAseq analysis of LPS treated primary human CD14+ monocytes and autologous neutrophils (PMN) allowed us to classify lncRNAs modulated by LPS in a cell type specific manner. Specifically 1186 lncRNAs modulated by LPS in a monocyte specific manner, whereas 466 lncRNAs selectively modulated by LPS only in PMN. Among the monocyte-specific lncRNAs we focused our attention on NRIR for the following reasons: NRIR is strongly upregulated by LPS in monocytes; NRIR was described as an interferon (IFN) dependent lncRNA able to negative regulate the expression of IFN-dependent genes in hepatoma cell line; in PMN, LPS does not trigger the interferon response nor it upregulates NRIR expression, thus suggesting that the two events might be causally linked; the role of NRIR in inflammation and particularly in monocytes response to LPS remains to be elucidated. Kinetic analysis showed that NRIR expression starts to be detectable in CD14+ monocytes 4 hours post LPS (100ng/mL) stimulation, and keeps increasing up to 16 hours. Remarkably, IFNa (1000 U/mL) is a stronger and more rapid inducer of NRIR expression, that starts at 2h and keeps increasing up to 16h. Subcellular fractionation of LPS-treated monocytes showed that NRIR localizes in the nuclear fraction. To gain insights into NRIR function, RNAseq data of LPS treated CD14+ monocytes were used for the Weighted Gene Co-expression Network Analysis (WGCNA) and the NRIR specific WGCNA module was created and analyzed. GO term analysis of the protein coding genes of NRIR module displays an enrichment of genes involved in several processes, among which type I IFN and viral response was of particular interest. Taken together, these experimental and in silico data hint for a possible of NRIR in the type I IFN response triggered by LPS in human monocytes. This hypothesis is currently under investigation by loss of function strategy.
|Titolo:||Characterization of NRIR function in LPS treated human CD14+ monocytes.|
|Data di pubblicazione:||2018|
|Appare nelle tipologie:||04.02 Abstract in Atti di convegno|