RNA-Seq transcriptomic profiling of primary murine microglia treated with LPS or LPS + IFNγ

Abstract

Microglia, the main resident immune cells in the CNS, are thought to participate in the pathogenesis of various neurological disorders. LPS and LPS + IFNγ are stimuli that are widely used to activate microglia. However, the transcriptomic profiles of microglia treated with LPS and LPS + IFNγ have not been properly compared. Here, we treated murine primary microglial cultures with LPS or LPS + IFNγ for 6 hours and then performed RNA-Sequencing. Gene expression patterns induced by the treatments were obtained by WGCNA and 11 different expression profiles were found, showing differential responses to LPS and LPS + IFNγ in many genes. Interestingly, a subset of genes involved in Parkinson’s, Alzheimer’s and Huntington’s disease were downregulated by both treatments. By DESeq analysis we found differentially upregulated and downregulated genes that confirmed LPS and LPS + IFNγ as inducers of microglial pro-inflammatory responses, but also highlighted their involvement in specific cell functions. In response to LPS, microglia tended to be more proliferative, pro-inflammatory and phagocytic; whereas LPS + IFNγ inhibited genes were involved in pain, cell division and, unexpectedly, production of some inflammatory mediators. In summary, this study provides a detailed description of the transcriptome of LPS- and LPS + IFNγ treated primary microglial cultures. It may be useful to determine whether these in vitro phenotypes resemble microglia in in vivo pathological conditions.

PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia

“…We investigated further LPS-IFN-γ effect since it simulates in vivo damage-associated molecular patterns acting on Toll-like receptors and IFN-γ produced by CNS cells (Pulido-Salgado et al., 2018). APPswe iMGLs produced less TNF-α and MCP1 in response to LPS-IFN-γ compared with control iMGLs (Figure 6B).…”

Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling

“…Accumulating evidence suggests that reactive microglia and astrocytosis (gliosis) play significant roles in neuroinflammation [2], and the activation of these glial cells releases several inflammatory cytokines, which eventually leads to neuroinflammation-mediated neurodegeneration [3]. Lipopolysaccharide (LPS) is a membrane component of Gram-negative bacteria [4], which activates the immune system and leads to behavioral and memory impairments, oxygen species (ROS) generation, lipid per oxidation (LPO), and consequently oxidative brain damage [5,6]. Previous studies suggest that dormant, non-growing bacteria are a crucial contributing factor in AD, and these bacteria release several inflammatory components such as LPS [3,7].…”

Construction and Analysis for Dysregulated lncRNAs and mRNAs in Lipopolysaccharide-Induced Porcine Peripheral Blood Mononuclear Cells

“…It was well recognized that a series of genes involved in LPS-induced in ammation [18][19][20]. In this study, the DE mRNAs functional enrichment results showed that these genes were related to some biological processes, including in ammatory response, immune response, cytokine activity, chemokine activity, cytokine-cytokine receptor interaction, TNF signal pathway, NF-κB signal pathway, JAK-STAT signal pathway, NOD-like receptor signal pathway and TLR signal pathway, which were closely associated with LPS-induced in ammation [21][22][23][24][25].…”