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TUTCRIS

Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells

Tutkimustuotosvertaisarvioitu

Standard

Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells. / Juuti-Uusitalo, Kati; Nieminen, Monica; Treumer, Felix; Ampuja, Minna; Kallioniemi, Anne; Klettner, Alexa; Skottman, Heli.

julkaisussa: Investigative Ophthalmology and Visual Science, Vuosikerta 56, Nro 11, 2015, s. 6265-6274.

Tutkimustuotosvertaisarvioitu

Harvard

Juuti-Uusitalo, K, Nieminen, M, Treumer, F, Ampuja, M, Kallioniemi, A, Klettner, A & Skottman, H 2015, 'Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells', Investigative Ophthalmology and Visual Science, Vuosikerta. 56, Nro 11, Sivut 6265-6274. https://doi.org/10.1167/iovs.15-17333

APA

Juuti-Uusitalo, K., Nieminen, M., Treumer, F., Ampuja, M., Kallioniemi, A., Klettner, A., & Skottman, H. (2015). Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells. Investigative Ophthalmology and Visual Science, 56(11), 6265-6274. https://doi.org/10.1167/iovs.15-17333

Vancouver

Juuti-Uusitalo K, Nieminen M, Treumer F, Ampuja M, Kallioniemi A, Klettner A et al. Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells. Investigative Ophthalmology and Visual Science. 2015;56(11):6265-6274. https://doi.org/10.1167/iovs.15-17333

Author

Juuti-Uusitalo, Kati ; Nieminen, Monica ; Treumer, Felix ; Ampuja, Minna ; Kallioniemi, Anne ; Klettner, Alexa ; Skottman, Heli. / Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells. Julkaisussa: Investigative Ophthalmology and Visual Science. 2015 ; Vuosikerta 56, Nro 11. Sivut 6265-6274.

Bibtex - Lataa

@article{bd2801fac2224015a04059885aa52faa,
title = "Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells",
abstract = "PURPOSE. In several retinal complications, such as age-dependent macular degeneration (AMD), oxidative stress is increased and cytokine level is elevated. These are shown to alter the activation and expression of matrix metalloproteinase (MMP) both in human primary and immortalized retinal pigment epithelial (RPE) cells. However, the effects on human embryonic stem cell (hESC)–derived RPE cells remain to be elucidated. METHODS. The mature hESC-RPE cells were exposed to inflammatory cytokines (IFN-γ or TNF-α) for 24 hours or oxidative stress (H2O2) for 1 hour. Effects on barrier properties were analyzed with transepithelial electrical resistance (TEER), the expression of MMP-1, MMP-2, MMP-3, MMP-9, collagen I, and collagen IV genes with quantitative RT-PCR, and the expression of MMP- 1 and MMP-3 proteins with Western blot or ELISA, respectively. Also, activation and secretion of MMP-2 and -9 proteins were analyzed with zymography. RESULTS. In normal state, mature hESC-RPE cells expressed MMP-1, -2, -3, and -9 genes in low levels, respectively. Tumor necrosis factor-α increased MMP-1 and -2 gene expression, and H2O2 increased MMP-3 and -9 gene expression. Zymography revealed IFN-γ– and TNF-α– induced secretion of MMP-2 and high-molecular-weight species of MMP (HMW MMP), but H2O2 decreased their secretion. Furthermore, TNF-α and H2O2 significantly decreased barrier properties. CONCLUSIONS. Here, cytokines induced the MMP-1 and -2 gene and protein expression. Also, H2O2 induced MMP-3 and -9 gene expression, but not their protein secretion. These data propose that under oxidative stress and cytokine stimuli, mature hESC-RPE cells resemble their native counterpart in the human eye in regard to MMP secretion and expression and could be used to model retinal disorders involving alterations in MMP activity such as AMD, diabetic retinopathy, or proliferative vitreoretinopathy in vitro.",
keywords = "Matrix metalloproteinase, MMP, Retinal pigment epithelium, Stem cells",
author = "Kati Juuti-Uusitalo and Monica Nieminen and Felix Treumer and Minna Ampuja and Anne Kallioniemi and Alexa Klettner and Heli Skottman",
year = "2015",
doi = "10.1167/iovs.15-17333",
language = "English",
volume = "56",
pages = "6265--6274",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology",
number = "11",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Effects of cytokine activation and oxidative stress on the function of the human embryonic stem cell–derived retinal pigment epithelial cells

AU - Juuti-Uusitalo, Kati

AU - Nieminen, Monica

AU - Treumer, Felix

AU - Ampuja, Minna

AU - Kallioniemi, Anne

AU - Klettner, Alexa

AU - Skottman, Heli

PY - 2015

Y1 - 2015

N2 - PURPOSE. In several retinal complications, such as age-dependent macular degeneration (AMD), oxidative stress is increased and cytokine level is elevated. These are shown to alter the activation and expression of matrix metalloproteinase (MMP) both in human primary and immortalized retinal pigment epithelial (RPE) cells. However, the effects on human embryonic stem cell (hESC)–derived RPE cells remain to be elucidated. METHODS. The mature hESC-RPE cells were exposed to inflammatory cytokines (IFN-γ or TNF-α) for 24 hours or oxidative stress (H2O2) for 1 hour. Effects on barrier properties were analyzed with transepithelial electrical resistance (TEER), the expression of MMP-1, MMP-2, MMP-3, MMP-9, collagen I, and collagen IV genes with quantitative RT-PCR, and the expression of MMP- 1 and MMP-3 proteins with Western blot or ELISA, respectively. Also, activation and secretion of MMP-2 and -9 proteins were analyzed with zymography. RESULTS. In normal state, mature hESC-RPE cells expressed MMP-1, -2, -3, and -9 genes in low levels, respectively. Tumor necrosis factor-α increased MMP-1 and -2 gene expression, and H2O2 increased MMP-3 and -9 gene expression. Zymography revealed IFN-γ– and TNF-α– induced secretion of MMP-2 and high-molecular-weight species of MMP (HMW MMP), but H2O2 decreased their secretion. Furthermore, TNF-α and H2O2 significantly decreased barrier properties. CONCLUSIONS. Here, cytokines induced the MMP-1 and -2 gene and protein expression. Also, H2O2 induced MMP-3 and -9 gene expression, but not their protein secretion. These data propose that under oxidative stress and cytokine stimuli, mature hESC-RPE cells resemble their native counterpart in the human eye in regard to MMP secretion and expression and could be used to model retinal disorders involving alterations in MMP activity such as AMD, diabetic retinopathy, or proliferative vitreoretinopathy in vitro.

AB - PURPOSE. In several retinal complications, such as age-dependent macular degeneration (AMD), oxidative stress is increased and cytokine level is elevated. These are shown to alter the activation and expression of matrix metalloproteinase (MMP) both in human primary and immortalized retinal pigment epithelial (RPE) cells. However, the effects on human embryonic stem cell (hESC)–derived RPE cells remain to be elucidated. METHODS. The mature hESC-RPE cells were exposed to inflammatory cytokines (IFN-γ or TNF-α) for 24 hours or oxidative stress (H2O2) for 1 hour. Effects on barrier properties were analyzed with transepithelial electrical resistance (TEER), the expression of MMP-1, MMP-2, MMP-3, MMP-9, collagen I, and collagen IV genes with quantitative RT-PCR, and the expression of MMP- 1 and MMP-3 proteins with Western blot or ELISA, respectively. Also, activation and secretion of MMP-2 and -9 proteins were analyzed with zymography. RESULTS. In normal state, mature hESC-RPE cells expressed MMP-1, -2, -3, and -9 genes in low levels, respectively. Tumor necrosis factor-α increased MMP-1 and -2 gene expression, and H2O2 increased MMP-3 and -9 gene expression. Zymography revealed IFN-γ– and TNF-α– induced secretion of MMP-2 and high-molecular-weight species of MMP (HMW MMP), but H2O2 decreased their secretion. Furthermore, TNF-α and H2O2 significantly decreased barrier properties. CONCLUSIONS. Here, cytokines induced the MMP-1 and -2 gene and protein expression. Also, H2O2 induced MMP-3 and -9 gene expression, but not their protein secretion. These data propose that under oxidative stress and cytokine stimuli, mature hESC-RPE cells resemble their native counterpart in the human eye in regard to MMP secretion and expression and could be used to model retinal disorders involving alterations in MMP activity such as AMD, diabetic retinopathy, or proliferative vitreoretinopathy in vitro.

KW - Matrix metalloproteinase

KW - MMP

KW - Retinal pigment epithelium

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=84943249379&partnerID=8YFLogxK

U2 - 10.1167/iovs.15-17333

DO - 10.1167/iovs.15-17333

M3 - Article

VL - 56

SP - 6265

EP - 6274

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 11

ER -