Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells

Academic Article


  • We have previously demonstrated that chloroquine may evoke inflammatory responses in the central nervous system by inducing expression of pro-inflammatory cytokines by astroglial cells. In this study, we further examined the molecular mechanism responsible for chloroquine-induced activation of NF-κB and subsequent expression of chemokines by astroglial cells. We observed that (1) chloroquine induced expression of chemokines such as CCL2 and CXCL8 in a dose- and time-dependent manner in human astroglial cells; (2) other lysosomotropic agents such as ammonium chloride and bafilomycin A1 had minimal effects on chemokine expression; (3) inhibition of NF-κB by MG-132 and TPCK suppressed chloroquine-induced mRNA expression of chemokines; (4) chloroquine increased the intracellular level of reactive oxygen species (ROS) in a dose- and time-dependent manner by human astroglial cells, but not by monocytic/microglial cells; (5) chloroquine-induced increase of intracellular ROS level was suppressed by pre-incubation with diphenyl iodonium (DPI) and N-acetyl cysteine (NAC); and (6) inhibition of chloroquine-induced ROS production by DPI or NAC suppressed chloroquine-mediated activation of NF-κB and subsequent mRNA expression of chemokines in astroglial cells. These results collectively suggest that chloroquine generates ROS, which is responsible for NF-κB activation and subsequent expression of pro-inflammatory chemokines in human astroglial cells. © 2004 Wiley-Liss, Inc.
  • Published In

  • Glia  Journal
  • Digital Object Identifier (doi)

    Author List

  • Pare J; Choi K; Jeong E; Kwon D; Benveniste EN; Choi C
  • Start Page

  • 9
  • End Page

  • 20
  • Volume

  • 47
  • Issue

  • 1