Type I interferon induces CX3CL1 (fractalkine) and CCL5 (RANTES) production in human pulmonary vascular endothelial cells

Clin Exp Immunol. 2012 Oct;170(1):94-100. doi: 10.1111/j.1365-2249.2012.04638.x.

Abstract

Type I interferon (IFN) medications cause various adverse reactions, including vascular diseases. Although an association between chemokines and vascular diseases has also been reported, the relationship between type I IFN and chemokines in vascular endothelial cells (VEC) remains unclear. To provide clues to pathogenesis of the diseases, we analysed the effects of type I IFN on chemokine production in human VEC. Type I IFN induced higher CX3CL1 (fractalkine) mRNA expression and protein secretion in pulmonary arterial VEC than in umbilical vein VEC. Type I IFN also induced CCL5 [regulated upon activation normal T cell expressed and secreted (RANTES)] production in VEC, especially in lung micro-VEC. IFN-β induced much higher chemokine production than IFN-α, and Janus protein tyrosine kinase (JAK) inhibitor I prevented type I IFN-induced chemokine secretion. Type I IFN-induced chemokines may be involved in the pathophysiology of pulmonary vascular diseases, and the JAK inhibitor may serve as a therapeutic option for these diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL5 / biosynthesis*
  • Chemokine CX3CL1 / biosynthesis*
  • Connective Tissue Diseases / immunology
  • Connective Tissue Diseases / pathology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / immunology
  • Enzyme Inhibitors / pharmacology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / immunology
  • Humans
  • Hypertension, Pulmonary / immunology*
  • Hypertension, Pulmonary / pathology
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects*
  • Interferon-beta / administration & dosage
  • Interferon-beta / adverse effects*
  • Janus Kinases / antagonists & inhibitors
  • Microscopy, Fluorescence

Substances

  • Chemokine CCL5
  • Chemokine CX3CL1
  • Enzyme Inhibitors
  • Interferon-alpha
  • Interferon-beta
  • Janus Kinases