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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
12:50

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

Published on: September 15, 2017

Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target

Theresa C Barnes1, David G Spiller, Marina E Anderson

  • 1School of Clinical Sciences, University of Liverpool, Liverpool, UK.

Annals of the Rheumatic Diseases
|November 12, 2010
PubMed

Insights

Systemic sclerosis serum triggers endothelial cell apoptosis and activation, primarily through interleukin-6 (IL-6) in the presence of neutrophils. This suggests IL-6 as a potential therapeutic target for systemic sclerosis.

Area of Science:

  • Immunology
  • Vascular Biology
  • Rheumatology

Background:

  • Systemic sclerosis (SSc) is a severe connective tissue disease with limited treatment options.
  • Endothelial cell activation and apoptosis are key factors in SSc pathogenesis, but underlying mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of endothelial cell-neutrophil interactions in SSc pathogenesis.
  • To identify the specific molecular mediators involved in SSc-induced endothelial cell dysfunction.

Main Methods:

  • Human dermal microvascular endothelial cells were co-cultured with neutrophils in the presence of healthy or SSc serum.
  • Endothelial cell apoptosis was assessed via annexin V-FITC binding.
  • Endothelial cell activation was measured by E-selectin expression using flow cytometry and confocal microscopy.

Main Results:

  • SSc serum significantly increased endothelial cell apoptosis and E-selectin expression compared to control serum, dependent on neutrophils.
  • Recombinant interleukin-6 (IL-6) mimicked these effects.
  • IL-6 neutralization and blockade of IL-6 trans-signalling (using soluble gp130) reduced SSc serum-induced endothelial cell activation and apoptosis.

Conclusions:

  • SSc serum induces endothelial cell activation and apoptosis in a neutrophil-dependent manner, largely mediated by IL-6.
  • These findings highlight IL-6 as a significant factor in SSc vascular pathology.
  • Targeting IL-6 presents a promising therapeutic strategy for systemic sclerosis.
Abstract

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