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- W3183246938 endingPage "831" @default.
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- W3183246938 abstract "Blood-retinal barrier (BRB) dysfunction underlies macular oedema in many sight-threatening conditions, including diabetic macular oedema, neovascular age-related macular degeneration and uveoretinitis. Inflammation plays an important role in BRB dysfunction. This study aimed to understand the role of the inflammatory cytokine IL-17A in BRB dysfunction and the mechanism involved. Human retinal pigment epithelial (RPE) cell line ARPE19 and murine brain endothelial line bEnd.3 were cultured on transwell membranes to model the outer BRB and inner BRB, respectively. IL-17A treatment (3 days in bEnd.3 cells and 6 days in ARPE19 cells) disrupted the distribution of claudin-5 in bEnd.3 cells and ZO-1 in ARPE19 cells, reduced the transepithelial/transendothelial electrical resistance (TEER) and increased permeability to FITC-tracers in vitro. Intravitreal (20 ng/1 μL/eye) or intravenous (20 ng/g) injection of recombinant IL-17A induced retinal albumin leakage within 48 h in C57BL/6J mice. Mechanistically, IL-17A induced Janus kinase 1 (JAK1) phosphorylation in bEnd.3 but not ARPE19 cells. Blocking JAK1 with Tofacitinib prevented IL-17A-mediated claudin-5 dysmorphia in bEnd.3 cells and reduced albumin leakage in IL-17A-treated mice. Our results suggest that IL-17A can damage the BRB through the activating the JAK1 signaling pathway, and targeting this pathway may be a novel approach to treat inflammation-induced macular oedema." @default.
- W3183246938 created "2021-08-02" @default.
- W3183246938 creator A5023333681 @default.
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- W3183246938 creator A5044907152 @default.
- W3183246938 creator A5046784348 @default.
- W3183246938 date "2021-07-16" @default.
- W3183246938 modified "2023-10-12" @default.
- W3183246938 title "IL-17A Damages the Blood–Retinal Barrier through Activating the Janus Kinase 1 Pathway" @default.
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- W3183246938 doi "https://doi.org/10.3390/biomedicines9070831" @default.
- W3183246938 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8301352" @default.
- W3183246938 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34356895" @default.