SENSITISATION OF THE IFN gamma-STAT1-SIGNALLING-PATHWAY IN RHEUMATOID ARTHRITIS MONOCYTES

Background Both, type I interferons (IFNα, IFNβ) and the type II IFN IFNγ signal via phosphorylating Stat1. Immunohistochemistry and gene expression signatures of synovial tissues suggest an activated IFN-Stat1-signalling-pathway in rheumatoid arthritis (RA). This study was performed to determine the activity of the IFN-Stat1-signalling-pathway in RA peripheral blood monocytes. Methods Flourocytometry or qPCR was used to measure the expression of Stat1, phospho-Stat1 (pStat1) and IFN-inducible genes, such as IP-10 and OAS in RA and healthy (HC) peripheral blood monocytes. To examine the significance of Stat1 and of the IFNγ-inducible chemokine MIG (monokine induced by IFNγ) were measured using fluorocytometry. Results Levels of Stat1 and pStat1 protein expression were significantly increased in RA monocytes when compared to HC (mfi 14.7±8.1 vs 8.0±3.9, p=0.0002; mfi 5.1±1.3 vs 3.2±0.7, p RA monocytes demonstrated a considerably higher increase in pStat1 and MIG levels upon IFNγ stimulation when compared to monocytes from HC (pStat1: +2.8±1.8 vs +1.5±1.1, p Conclusions Consistent with a systemic proinflammatory activity of RA monocytes, these studies suggest activation of the IFNγ-Stat1-signalling pathway in RA.