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

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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)-beta, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta 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 A(1) 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.
Publisher
BLACKWELL PUBLISHING LTD
Issue Date
2003
Language
English
Article Type
Article
Keywords

TUMOR-NECROSIS-FACTOR; SPINAL-CORD INJURY; TRANSGENIC MICE; FACTOR-ALPHA; TNF-ALPHA; SIGNALING PATHWAYS; ALZHEIMERS-DISEASE; PROTEIN-KINASE; T-CELLS; ASTROCYTES

Citation

JOURNAL OF NEUROCHEMISTRY, v.84, no.6, pp.1266 - 1274

ISSN
0022-3042
DOI
10.1046/j.1471-4159.2003.01623.x
URI
http://hdl.handle.net/10203/82990
Appears in Collection
BiS-Journal Papers(저널논문)
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