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Activation of the JAK?STAT intracellular pathway in human retinal pigment epithelialcell line ARPE-19

Fasler-Kan, E. and Barteneva, N. and Ketterer, S. and Wunderlich, K. and Huwyler, J. and Gygax, D. and Flammer, J. and Meyer, P.. (2010) Activation of the JAK?STAT intracellular pathway in human retinal pigment epithelialcell line ARPE-19. International Journal of Interferon, Cytokine and Mediator Research, Vol. 2. pp. 127-136.

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Official URL: http://edoc.unibas.ch/dok/A5841670

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Abstract

Background: Retinal pigment epithelial cells constitute an important component of theblood–retinal barrier and play a pivotal role in the development of age-related maculardegeneration (AMD). Understanding the underlying molecular mechanisms is a prerequisitefor developing therapeutic strategies for the treatment of this disease. This study investigatedcytokine-induced changes of the JAK–STAT (Janus tyrosine kinase–signal transducers andactivators of transcription) signaling pathway in the human retinal pigment epithelial cell lineARPE-19 and potential implications for AMD.Methods: Electromobility shift assay, immunofluorescence staining, and flow cytometry wereused to evaluate the JAK–STAT pathway in the ARPE-19 cell line.Results: We examined cytokine-induced expression of STATs in the ARPE-19 cell line. StrongSTAT1 activation determined by electromobility shift assay and flow cytometry was demonstratedupon exposure to interferon-γ. Interferon-α upregulated STAT1, STAT2, and STAT3 inARPE-19 cells, while interleukin-6 (IL-6) and IL-4 activated STAT3 and STAT6, respectively.Confocal microscopy identified the nuclear translocation of the STAT proteins. Flow cytometryanalysis demonstrated the upregulation of major histocompatibility complex molecules onARPE-19 cells as responses to interferon-α and interferon-γ.Conclusion: Our data demonstrate the upregulation of members of the JAK–STAT signalingpathway in the ARPE-19 cells upon stimulation with interferon-α, interferon-γ, IL-4, and IL-6.We present a model for these signaling pathways potentially relevant for AMD, which mayprove useful for screening of AMD therapeutics.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Huwyler, Jörg
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Dove Medical Press
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:08 Jun 2012 06:56
Deposited On:08 Jun 2012 06:51

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