Chemokines and their receptors in the CNS: expression of CXCL12/SDF-1 and CXCR4 and their role in astrocyte proliferation

Toxicol Lett. 2003 Apr 4;139(2-3):181-9. doi: 10.1016/s0378-4274(02)00432-0.

Abstract

The study of chemokine role in the CNS indubitably represents an important step to understanding many aspects of brain pathology, physiology and development. Here we discuss our recent research on the expression of chemokines and chemokine receptors in brain tissues and in cultured CNS cells, with particular regard to the CXCL12/SDF-1-CXCR4 system. We showed their expression in both glial and neuronal cells in basal conditions and their modulation upon stimulation. We demonstrated that CXCL12/SDF-1 in vitro act as a growth factor for astrocytes by stimulating their proliferation, a phenomenon that could represent the basis of pathological conditions such as gliosis and malignant transformation. We investigated the signal transduction pathways, identifying in the sequential activation of G-protein-PI-3Kinase-ERK1/2 the main signaling cascade linked to the CXCL12/SDF-1-induced proliferation in astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / metabolism*
  • Cell Division
  • Central Nervous System / cytology*
  • Central Nervous System / metabolism*
  • Chemokine CXCL12
  • Chemokines / metabolism*
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Gene Expression Regulation*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*

Substances

  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • RNA, Messenger
  • Receptors, CXCR4