STAT1 and IRF8 orchestrate IFNγ and LPS-mediated signal integration in the vasculature that leads to amplified pro-atherogenic responses

The transcription factor Signal Transducer and Activator of Transcription (STAT) 1 is activated by Interferon gamma (IFNγ) but also Lipopolysaccharide (LPS) is the trigger of inflammation. STAT1 together with downstream activated Interferon Regulatory Factors (IRF) create a platform for signal integration between IFNγ and the Toll-Like Receptor (TLR) 4 ligand in immune cells. Little is known about the role of STAT1 and IRFs on potential synergism between LPS- and INFγ-signaling in cells from the vasculature. We investigated whether vascular cells can promote inflammatory signaling by the STAT1-IRFs pathway. To study signal integration between LPS and IFNγ pathways and the role of STAT1, aortic Vascular Smooth Muscle Cells (VSMCs) from C57BL/6 and STAT1 mice were isolated and treated either with IFNγ or LPS or pretreated with IFNγ followed by LPS. Experiment was prepared in three independent biological repeats for each cell type.