Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ
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Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ. / Faber, Carsten; Juel, Helene Bæk; Jensen, Benjamin Anderschou Holbech; Christensen, Jan Pravsgaard; Prause, Jan Ulrik; Thomsen, Allan Randrup; Nissen, Mogens Holst.
I: Investigative Ophthalmology & Visual Science, Bind 60, Nr. 1, 2019, s. 192-201.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Chemokine Expression in Murine RPE/Choroid in Response to Systemic Viral Infection and Elevated Levels of Circulating Interferon-γ
AU - Faber, Carsten
AU - Juel, Helene Bæk
AU - Jensen, Benjamin Anderschou Holbech
AU - Christensen, Jan Pravsgaard
AU - Prause, Jan Ulrik
AU - Thomsen, Allan Randrup
AU - Nissen, Mogens Holst
PY - 2019
Y1 - 2019
N2 - Purpose: To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface.Methods: Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level.Results: Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-γ resulted in increased expression of chemokine ligands, chemokine receptors, and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/β receptor or IFN-γ.Conclusions: Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, AMD, and diabetes.
AB - Purpose: To examine how circulating immune mediators in vivo may affect gene and protein expression at the RPE/choroid interface.Methods: Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with IFN-γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level.Results: Both the systemic immune activation from virus infection and the sterile systemically increased level of IFN-γ resulted in increased expression of chemokine ligands, chemokine receptors, and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/β receptor or IFN-γ.Conclusions: Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, AMD, and diabetes.
U2 - 10.1167/iovs.18-25721
DO - 10.1167/iovs.18-25721
M3 - Journal article
C2 - 30654385
VL - 60
SP - 192
EP - 201
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
SN - 0146-0404
IS - 1
ER -
ID: 212166751