mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
Interleukin 2 Activates Brain Microvascular Endothelial Cells Resulting in
Destabilization of Adherens Junctions.
Authors Wylezinski LS, Hawiger J
Submitted By Submitted Externally on 12/6/2016
Status Published
Journal The Journal of biological chemistry
Year 2016
Date Published 10/28/2016
Volume : Pages 291 : 22913 - 22923
PubMed Reference 27601468
Abstract The pleiotropic cytokine interleukin 2 (IL2) disrupts the blood-brain barrier
and alters brain microcirculation, underlying vascular leak syndrome that
complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also
play a role in the development of multiple sclerosis and other chronic
neurological disorders. The mechanism of IL2-induced disruption of brain
microcirculation has not been determined previously. We found that both human
and murine brain microvascular endothelial cells express constituents of the IL2
receptor complex. Then we established that signaling through this receptor
complex leads to activation of the transcription factor, nuclear factor ?B,
resulting in expression of proinflammatory interleukin 6 and monocyte
chemoattractant protein 1. We also discovered that IL2 induces disruption of
adherens junctions, concomitant with cytoskeletal reorganization, ultimately
leading to increased endothelial cell permeability. IL2-induced phosphorylation
of vascular endothelial cadherin (VE-cadherin), a constituent of adherens
junctions, leads to dissociation of its stabilizing adaptor partners,
p120-catenin and ß-catenin. Increased phosphorylation of VE-cadherin was also
accompanied by a reduction of Src homology 2 domain-containing protein-tyrosine
phosphatase 2, known to maintain vascular barrier function. These results
unravel the mechanism of deleterious effects induced by IL2 on brain
microvascular endothelial cells and may inform the development of new measures
to improve IL2 cancer immunotherapy, as well as treatments for autoimmune
diseases affecting the central nervous system.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.