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- Title
Influence of proinflammatory stimuli on the expression of vascular ribonuclease 1 in endothelial cells.
- Authors
Gansler, Julia; Preissner, Klaus T.; Fischer, Silvia
- Abstract
Extracellular RNA (eRNA) released under injury or pathological conditions has been identified as a yet unrecognized vascular alarm signal to induce procoagulant, permeability-promoting, and pro-inflammatory activities, eRNA-induced functions were largely prevented by administration of RNasel as natural blood vessel-protective antagonist of eRNA. The aim of this study was to investigate the inflammatory regulation of endothelial cell RNasel, which is partly stored in Weibel-Palade bodies of these cells. Long-term treatment of human umbilical vein endothelial cells (HUVECs) with inflammatory agents like tumor necrosis factor α (TNF-α) or interleukin 1β (IL-1β), but not with eRNA, significantly decreased the release (34±5%; 34±7% of control) as well as the cellular expression (19.5±5%; 33±8% of control) of RNasel. Down-regulation of RNasel by TNF- α stimulation or RNasel siRNA knockdown increased the permeability of HUVEC monolayers, demonstrated dearrangement of VE-cadherins at cell-cell borders Mechanistically, cytokine-induced decrease of RNasel expression did not involve the nuclear factor κ B (NFκB) signaling pathway but epigenic modifications Since inhibition of histone deacetylases resulted in recovery of RNasel expression and secretion after cytokine treatment, an acetylation-dependent process of RNasel regulation is proposed. These results indicate that cytokine-mediated down-regulation of RNasel in endothelial cells may aggravate eRNA-induced inflammatory activities and thereby disturbs the vascular homeostasis of the extracellular RNA/RNase system.
- Subjects
ENDOTHELIAL cells; RIBONUCLEASES; TUMOR necrosis factors; HISTONE deacetylase; HOMEOSTASIS; THERAPEUTIC use of cytokines
- Publication
FASEB Journal, 2014, Vol 28, Issue 2, p752
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.13-238600