Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Cocaine is known to facilitate the transmigration of inflammatory leukocytes into the brain, an important mechanism underlying neuroinflammation. Pericytes are well-recognized as important constituents of the blood–brain barrier (BBB), playing a key role in maintaining barrier integrity. In the present study, we demonstrate for the first time that exposure of human brain vascular pericytes to cocaine results in enhanced secretion of CXCL10, leading, in turn, to increased monocyte transmigration across the BBB both in vitro and in vivo. This process involved translocation of σ-1 receptor (σ-1R) and interaction of σ-1R with c-Src kinase, leading to activation of the Src–PDGFR-β–NF-κB pathway. These findings imply a novel role for pericytes as a source of CXCL10 in the pericyte–monocyte cross talk in cocaine-mediated neuroinflammation, underpinning their role as active components of the innate immune responses.
Funding Information
  • National Institutes of Health
  • National Institute on Drug Abuse (DA035203, DA040397, DA041751, DA044586, DA043138, DA046831, DA042704)
  • National Institute of Mental Health (MH106425, MH112848)
  • Nebraska Center for Substance Abuse Research
  • National Institutes of Health
  • National Institute of Mental Health (2P30MH062261)
  • National Institutes of Health

This publication has 76 references indexed in Scilit: