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- Title
Chloroquine induces activation of nuclear factor-κB and subsequent expression of pro-inflammatory cytokines by human astroglial cells.
- Authors
Park, Jinseu; Kwon, Daeho; Choi, Chulhee; Oh, Jae-Wook; Benveniste, Etty N.
- Abstract
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 pro-inflammatory 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.
- Subjects
CHLOROQUINE; AUTOIMMUNE disease treatment; TREATMENT of neurodegeneration
- Publication
Journal of Neurochemistry, 2003, Vol 84, Issue 6, p1266
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.01623.x