Effect of SOCS1 overexpression on RPE cells activated by cytokines

Abstract

AbstractPurpose Retinal pigmented epithelium (RPE) cell activation by cytokines plays an important role in autoimmune uveitis development. The aim of this study was to investigate if Suppressors of Cytokine Signaling (SOCS1) overexpression in RPE cells can modulate this activation.Methods SOCS clone and control clone were isolated after stable transfection of APRE‐19 with plasmids containing or not the SOCS1 gene. qRT‐PCR was used to measure SOCS1 mRNA expression. Clones were stimulated by IFNγ or/and TNFα. Membrane expression of MHCII and CD54 was measured by flow cytometry, IL‐8 secretion by ELISA and (P‐)STAT‐1 and IκBα expression by Western Blot.Results We found a stable high expression of SOCS1 in the SOCS clone as compared to the control clone or native ARPE cells. This SOCS1 overexpression strongly decreased IFNγ‐mediated STAT‐1 phosphorylation, MHCII induction and CD54 upregulation. On the contrary, SOCS1 overexpression had no effect on TNFα‐mediated IκBα degradation, IL‐8 upregulation, but weakly inhibited CD54 upregulation. During simultaneous IFNγ and TNFα stimulation, SOCS1 overexpression canceled the inhibitory effect of IFNγ on TNFα‐induction of IL‐8 secretion.Conclusion SOCS1 overexpression can block IFNγ but have almost no effect on TNFα activation of retinal pigmented epithelium cells. Those data suggest that SOCS1 overexpression might only affect certain cytokine pathways important in autoimmune uveitis development.