Abstract
Background: Retinal pigment epithelial cells constitute an important component of the blood-retinal barrier and play a pivotal role in the development of age-related macular degeneration (AMD). Understanding the underlying molecular mechanisms is a prerequisite for developing therapeutic strategies for the treatment of this disease. This study investigated cytokine-induced changes of the JAK-STAT (Janus tyrosine kinase-signal transducers and activators of transcription) signaling pathway in the human retinal pigment epithelial cell line ARPE-19 and potential implications for AMD. Methods: Electromobility shift assay, immunofluorescence staining, and flow cytometry were used 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. Strong STAT1 activation determined by electromobility shift assay and flow cytometry was demonstrated upon exposure to interferon-γ. Interferon-α upregulated STAT1, STAT2, and STAT3 in ARPE-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 cytometry analysis demonstrated the upregulation of major histocompatibility complex molecules on ARPE-19 cells as responses to interferon-α and interferon-γ. Conclusion: Our data demonstrate the upregulation of members of the JAK-STAT signaling pathway 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 may prove useful for screening of AMD therapeutics.
| Original language | English |
|---|---|
| Pages (from-to) | 127-136 |
| Number of pages | 10 |
| Journal | International Journal of Interferon, Cytokine and Mediator Research |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 |
| Externally published | Yes |
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Keywords
- Age-related macular degeneration
- ARPE-19
- JAK-STAT pathway
- Retinal pigment epithelium
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Activation of the JAK-STAT intracellular pathway in human retinal pigment epithelial cell line ARPE-19. / Fasler-Kan, Elizaveta; Barteneva, Natasha; Ketterer, Sylvia; Wunderlich, Kerstin; Huwyler, Jörg; Gygax, Daniel; Flammer, Josef; Meyer, Peter.
In: International Journal of Interferon, Cytokine and Mediator Research, Vol. 2, No. 1, 2010, p. 127-136.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of the JAK-STAT intracellular pathway in human retinal pigment epithelial cell line ARPE-19
AU - Fasler-Kan, Elizaveta
AU - Barteneva, Natasha
AU - Ketterer, Sylvia
AU - Wunderlich, Kerstin
AU - Huwyler, Jörg
AU - Gygax, Daniel
AU - Flammer, Josef
AU - Meyer, Peter
PY - 2010
Y1 - 2010
N2 - Background: Retinal pigment epithelial cells constitute an important component of the blood-retinal barrier and play a pivotal role in the development of age-related macular degeneration (AMD). Understanding the underlying molecular mechanisms is a prerequisite for developing therapeutic strategies for the treatment of this disease. This study investigated cytokine-induced changes of the JAK-STAT (Janus tyrosine kinase-signal transducers and activators of transcription) signaling pathway in the human retinal pigment epithelial cell line ARPE-19 and potential implications for AMD. Methods: Electromobility shift assay, immunofluorescence staining, and flow cytometry were used 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. Strong STAT1 activation determined by electromobility shift assay and flow cytometry was demonstrated upon exposure to interferon-γ. Interferon-α upregulated STAT1, STAT2, and STAT3 in ARPE-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 cytometry analysis demonstrated the upregulation of major histocompatibility complex molecules on ARPE-19 cells as responses to interferon-α and interferon-γ. Conclusion: Our data demonstrate the upregulation of members of the JAK-STAT signaling pathway 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 may prove useful for screening of AMD therapeutics.
AB - Background: Retinal pigment epithelial cells constitute an important component of the blood-retinal barrier and play a pivotal role in the development of age-related macular degeneration (AMD). Understanding the underlying molecular mechanisms is a prerequisite for developing therapeutic strategies for the treatment of this disease. This study investigated cytokine-induced changes of the JAK-STAT (Janus tyrosine kinase-signal transducers and activators of transcription) signaling pathway in the human retinal pigment epithelial cell line ARPE-19 and potential implications for AMD. Methods: Electromobility shift assay, immunofluorescence staining, and flow cytometry were used 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. Strong STAT1 activation determined by electromobility shift assay and flow cytometry was demonstrated upon exposure to interferon-γ. Interferon-α upregulated STAT1, STAT2, and STAT3 in ARPE-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 cytometry analysis demonstrated the upregulation of major histocompatibility complex molecules on ARPE-19 cells as responses to interferon-α and interferon-γ. Conclusion: Our data demonstrate the upregulation of members of the JAK-STAT signaling pathway 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 may prove useful for screening of AMD therapeutics.
KW - Age-related macular degeneration
KW - ARPE-19
KW - JAK-STAT pathway
KW - Retinal pigment epithelium
UR - http://www.scopus.com/inward/record.url?scp=78649358648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649358648&partnerID=8YFLogxK
U2 - 10.2147/IJICMR.S13642
DO - 10.2147/IJICMR.S13642
M3 - Article
AN - SCOPUS:78649358648
VL - 2
SP - 127
EP - 136
JO - International Journal of Interferon, Cytokine and Mediator Research
JF - International Journal of Interferon, Cytokine and Mediator Research
SN - 1179-139X
IS - 1
ER -