Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines

Autor: M Bazewicz, Dafina Draganova, Catherine Bruyns, Liliane Tenenbaum, Abdel Chtarto, Francois Willermain, V Elmaleh, Maya Makhoul, Laure Caspers
Rok vydání: 2016
Předmět:
0301 basic medicine
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
Retinal Pigment Epithelium
Proinflammatory cytokine
Uveitis
Interferon-gamma
03 medical and health sciences
Suppressor of Cytokine Signaling 1 Protein
0302 clinical medicine
NF-KappaB Inhibitor alpha
medicine
Secretion
RNA
Messenger
STAT1
Interleukin 8
Retinal pigment epithelium
biology
Tumor Necrosis Factor-alpha
Suppressor of cytokine signaling 1
General Neuroscience
Interleukin-17
Interleukin-8
Histocompatibility Antigens Class II
Intercellular Adhesion Molecule-1
Molecular biology
IκBα
030104 developmental biology
medicine.anatomical_structure
030221 ophthalmology & optometry
biology.protein
Cytokines
Cell activation
Zdroj: Neuroscience letters, vol. 630, pp. 209-215
ISSN: 0304-3940
DOI: 10.1016/j.neulet.2016.07.054
Popis: 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.
Databáze: OpenAIRE
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