Expression of IRG1 in Microglia and its Effects on Hif1α and IRF7

Upon exposure to LPS and IFNγ, IRG1 (immune-responsive gene 1) expression highly increases in macrophages and microglia. It regulates immunometabolism in the cell and so is involved in metabolic and inflammatory changes cells go through under inflammatory conditions. Some of the major transcription factors that regulate cell metabolism and inflammatory response are Hif1α (hypoxia inducible factor 1 subunit alpha) and IRF7 (Interferon regulatory factor 7) and the relationship between these transcription factors and IRG1 is not well understood. The aim of our study was to investigate whether IRG1 has an effect on the expression of Hif1α and IRF7. BV-2 mouse microglia cells were stimulated with TLR4, TLR3, and TLR7 agonists (LPS, loxoribine, and poly-(I:C) respectively) IRG1 expression was measured by western blot. To test the effect of IRG1 on the expression of Hif1a and IRF7 we utilized siRNA to silence IRG1. Expression of Hif1α and IRF7 were detected by immunofluorescence. IRG1 expression was significantly upregulated in microglia, stimulated by LPS and loxoribine. LPS also increased the expression of Hif1α and IRF7 while loxoribine only increased the expression of Hif1α. IRG1 silencing also shows a tendency to decrease Hif1α expression but has no effect on IRF7 expression. IRG1 is upregulated in BV-2 microglia after TLR4 and TLR7 stimulation. Hif1α but not IRF7 expression is partially controlled by IRG1 in BV-2 cells during inflammation.