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Type I Interferons induce endothelial destabilization in Systemic Lupus Erythematosus in a Tie2-dependent manner.
Rafael-Vidal, Carlos; Martínez-Ramos, Sara; Malvar-Fernández, Beatriz; Altabás-González, Irene; Mouriño, Coral; Veale, Douglas J; Floudas, Achilleas; Fearon, Ursula; Reigosa, José María Pego; García, Samuel.
Afiliación
  • Rafael-Vidal C; Rheumatology and Immune-mediated Diseases Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Vigo, Spain.
  • Martínez-Ramos S; Rheumatology Department, University Hospital of Vigo, Vigo, Spain.
  • Malvar-Fernández B; Rheumatology and Immune-mediated Diseases Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Vigo, Spain.
  • Altabás-González I; Rheumatology Department, University Hospital of Vigo, Vigo, Spain.
  • Mouriño C; Rheumatology and Immune-mediated Diseases Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Vigo, Spain.
  • Veale DJ; Rheumatology Department, University Hospital of Vigo, Vigo, Spain.
  • Floudas A; Rheumatology and Immune-mediated Diseases Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Vigo, Spain.
  • Fearon U; Rheumatology Department, University Hospital of Vigo, Vigo, Spain.
  • Reigosa JMP; Rheumatology and Immune-mediated Diseases Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Vigo, Spain.
  • García S; Molecular Rheumatology, Clinical Medicine, Trinity Biomedical Science Institute, Dublin, Ireland.
Front Immunol ; 14: 1277267, 2023.
Article en En | MEDLINE | ID: mdl-38162654
ABSTRACT
Endothelial cell (EC) dysfunction is a hallmark of Systemic Lupus Erythematosus (SLE) and Tie2 is a receptor essential for vascular stability. Inflammatory processes promote inhibition of Tie2 homeostatic activation, driving vascular dysfunction. In this work we determined whether type I Interferons (IFN) induce Tie2 signalling-mediated endothelial dysfunction in patients with SLE. Serum levels of Angiopoietin (Ang)-1, Ang-2 and soluble (s)Tie1 in patients with SLE and healthy controls were measured by ELISA. Monocytes from patients with SLE and Human Umbilical Vein EC (HUVEC) were stimulated with IFN-α, IFN-ß (1000 I.U.) or SLE serum (20%). mRNA and protein expression, phosphorylation and translocation were determined by quantitative PCR, ELISA, Western Blot, flow cytometry and confocal microscopy. Viability and angiogenic capacity were determined by calcein and tube formation assays. We found that sTie1 and Ang-2 serum levels were increased and Ang-1 decreased in patients with SLE and were associated with clinical characteristics. Type I IFN significantly decreased Ang-1 and increased Ang-2 in monocytes from patients with SLE. Type I IFN increased sTie1 and Ang-2 secretion and reduced Tie2 activation in HUVEC. Functionally, type I IFN significantly reduced EC viability and impaired angiogenesis in a Tie2 signalling-dependent manner. Finally, SLE serum increased Ang-2 and sTie1 secretion and significantly decreased tube formation. Importantly, Tie1 and IFNAR1 knockdown reversed these effects in tube formation. Overall, type I IFN play an important role in the stability of EC by inhibiting Tie2 signalling, suggesting that these processes may be implicated in the cardiovascular events observed in patients with SLE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Receptor TIE-2 / Lupus Eritematoso Sistémico Límite: Humans Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón Tipo I / Receptor TIE-2 / Lupus Eritematoso Sistémico Límite: Humans Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza