Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.
Détails
Télécharger: BIB_2D23E59D94BD.P001.pdf (1164.64 [Ko])
Etat: Public
Version: Author's accepted manuscript
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_2D23E59D94BD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.
Périodique
Neuroscience letters
ISSN
1872-7972 (Electronic)
ISSN-L
0304-3940
Statut éditorial
Publié
Date de publication
06/09/2016
Peer-reviewed
Oui
Volume
630
Pages
209-215
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
04/08/2016 18:33
Dernière modification de la notice
20/08/2019 14:12