LPS-induced lncRNA expression profiling in human PBMC-derived macrophages

We performed human lncRNA microarray analysis in LPS-stimulated primary human macrophages. We then carried out loss-of-function and gain-of-function experiments, luciferase reporter assays, RNA pulldown, RNA immunoprecipitation, and mouse endotoxemia studies, including humanized mouse models. Results: We identified 11 lncRNAs that were significantly increased by LPS.

Among them, lnc-FAM164A1 was selected for further study. Silencing of lnc-FAM164A1 by antisense oligonucleotides or siRNA reduced the LPS-induced expression of pro-inflammatory cytokines, including CCL2, IL-6, and TNF-a. In contrast, enforced expression of lnc FAM164A1 enhanced inflammatory responses in human and mouse macrophages. lnc FAM164A1 also promoted NF-kB-related signaling.

RNA pulldown and RNA immunoprecipitation identified ACLY as an lnc-FAM164A1- associated protein. ACLY silencing reduced the inflammatory effects induced by lnc-FAM164A1. Discussion: These findings support that human lnc-FAM164A1 promotes pro-inflammatory activation of macrophages through its interaction with ACLY and NF-kB-related signaling.