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

Details

Ressource 1Download: BIB_2D23E59D94BD.P001.pdf (1164.64 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_2D23E59D94BD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.
Journal
Neuroscience letters
Author(s)
Bazewicz M., Draganova D., Makhoul M., Chtarto A., Elmaleh V., Tenenbaum L., Caspers L., Bruyns C., Willermain F.
ISSN
1872-7972 (Electronic)
ISSN-L
0304-3940
Publication state
Published
Issued date
06/09/2016
Peer-reviewed
Oui
Volume
630
Pages
209-215
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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
Cells, Cultured, Cytokines/metabolism, Histocompatibility Antigens Class II/metabolism, Humans, Intercellular Adhesion Molecule-1/metabolism, Interferon-gamma/metabolism, Interleukin-17/metabolism, Interleukin-8/metabolism, NF-KappaB Inhibitor alpha/metabolism, Phosphorylation, RNA, Messenger/metabolism, Retinal Pigment Epithelium/metabolism, STAT1 Transcription Factor, Suppressor of Cytokine Signaling 1 Protein/metabolism, Tumor Necrosis Factor-alpha/metabolism, Uveitis/metabolism, ,IL-17, IFNγ, IL-8, RPE, SOCS1, UVEITIS
Pubmed
Web of science
Open Access
Yes
Create date
04/08/2016 17:33
Last modification date
20/08/2019 13:12
Usage data