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

Fang Niu, Ke Liao, Guoku Hu, Susmita Sil, Shannon Callen, Ming Lei Guo, Lu Yang, Shilpa Buch

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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 frst 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. Tis process involved translocation of s-1 receptor (s-1R) and interaction of s-1R with c-Src kinase, leading to activation of the Src-PDGFR-β-NF-κB pathway. Tese fndings 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.

Original languageEnglish (US)
Pages (from-to)700-721
Number of pages22
JournalJournal of Cell Biology
Volume218
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

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ASJC Scopus subject areas

  • Cell Biology

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