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Neurosci Lett. 2016 Sep 6;630:209-215. doi: 10.1016/j.neulet.2016.07.054. Epub 2016 Jul 29.

Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.

Author information

1
I.R.I.B.H.M (Institute of Interdisciplinary Research), Université Libre De Bruxelles Campus Erasme, Brussels, Belgium; Department of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium. Electronic address: mbazewic@ulb.ac.be.
2
I.R.I.B.H.M (Institute of Interdisciplinary Research), Université Libre De Bruxelles Campus Erasme, Brussels, Belgium; Department of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium.
3
I.R.I.B.H.M (Institute of Interdisciplinary Research), Université Libre De Bruxelles Campus Erasme, Brussels, Belgium.
4
Department of Ophthalmology, CHU St-Pierre and Brugmann, Brussels, Belgium.
5
Clinical Neurosciences Department, Lausanne University Hospital, Lausanne, Switzerland.

Abstract

The purpose of this study was to investigate the in vitro effect of Suppressor Of Cytokine Signaling 1 (SOCS1) overexpression in retinal pigment epithelium (RPE) cells on their activation by pro-inflammatory cytokines IFNγ, TNFα and IL-17. Retinal pigment epithelium cells (ARPE-19) were stably transfected with the control plasmid pIRES2-AcGFP1 or the plasmid pSOCS1-IRES2-AcGFP1. They were stimulated by IFNγ (150ng/ml), TNFα (30ng/ml) or IL-17 (100ng/ml). The levels of SOCS1 mRNA were measured by real-time PCR. Signal Transducer and Activator of Transcription 1 (STAT1) phosphorylation and IκBα expression were analysed by western Blot (WB). IL-8 secretion was analysed by ELISA and expression of MHCII molecules and ICAM-1/CD54 by flow cytometry. Our data show that SOCS1 mRNA overexpression in RPE cells prevents IFNγ-induced SOCS1 mRNA increase and IFNγ-mediated STAT1 phosphorylation. Moreover, SOCS1 overexpression in RPE cells inhibits IFNγ-induced decrease of IL-8 secretion and prevents IFNγ-induced MHC II and ICAM1/CD54 upregulation. However, SOCS1 overexpression does not affect TNFα-induced IκBα degradation nor block TNFα-induced or IL-17-induced IL-8 secretion. On the contrary, IL-17-induced secretion is increased by SOCS1 overexpression. In conclusion, SOCS1 overexpression in RPE cells inhibits some IFNγ-mediated responses that lead to uveitis development. This notion raises the possibility that SOCS1 overexpression could be a novel target for treating non-infectious uveitis. However, some proinflammatory effects of TNFα and IL-17 stimulation on RPE are not blocked by SOCS1 overexpression.

KEYWORDS:

,IL-17; IFNγ; IL-8; RPE; SOCS1; UVEITIS

PMID:
27478014
DOI:
10.1016/j.neulet.2016.07.054
[Indexed for MEDLINE]
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