Chloroquine induces activation of nuclear factor-κB and subsequent expression of pro-inflammatory cytokines by human astroglial cells

Academic Article

Abstract

  • Chloroquine, an antimalarial lysosomotropic base, is known for its anti-inflammatory effects and therefore used for treatment of autoimmune diseases. Given its anti-inflammatory effects, it has been under clinical trials to modify neurodegenerative processes. In this study, we examined whether chloroquine has an anti-inflammatory effect in the CNS by determining the in vitro effects of chloroquine on LPS-induced expression of cytokines by glial cells. We observed that (i) chloroquine augmented LPS-induced expression of proinflammatory cytokines such as lymphotoxin (LT)-β, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β and IL-6 in human astroglial cells, while the same treatment suppressed LPS-induced expression of cytokines in monocytic and microglial cells; (ii) chloroquine alone induced expression of pro-inflammatory cytokines in a dose- and time-dependent manner in astroglial cells; (iii) other lysosomotropic agents such as ammonium chloride and bafilomycin A1 had minimal effects on cytokine expression; and (iv) chloroquine induced the activation of nuclear factor-kappa B in astroglial cells, which is a required component of chloroquine induction of cytokines. These results suggest that chloroquine may evoke either anti- or pro-inflammatory responses in the CNS depending on the cellular context.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Park J; Kwon D; Choi C; Oh JW; Benveniste EN
  • Start Page

  • 1266
  • End Page

  • 1274
  • Volume

  • 84
  • Issue

  • 6