TY - JOUR
T1 - Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS
AU - Niu, Fang
AU - Liao, Ke
AU - Hu, Guoku
AU - Sil, Susmita
AU - Callen, Shannon
AU - Guo, Ming Lei
AU - Yang, Lu
AU - Buch, Shilpa
N1 - Funding Information:
This work was supported by National Institutes of Health, National Institute on Drug Abuse grants DA035203, DA040397, DA041751, DA044586 (to S. Buch); DA043138 (to S. Buch and G. Hu); and DA046831 and DA042704 (to G. Hu); and National Institute of Mental Health grants MH106425 (to S. Buch) and MH112848 (to S. Buch and G. Hu), as well as the Nebraska Center for Substance Abuse Research. The project was supported by National Institutes of Health, National Institute of Mental Health grant 2P30MH062261. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing financial interests.
Publisher Copyright:
© 2018 Sawyer et al.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201712011
DO - 10.1083/jcb.201712011
M3 - Article
C2 - 30626719
AN - SCOPUS:85061131875
SN - 0021-9525
VL - 218
SP - 700
EP - 721
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -