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Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages

Bondeson, J and Sundler, Roger LU (1998) In General Pharmacology 30(3). p.66-357
Abstract
1. The effects of antimalarial drugs on the intracellular signaling leading to activation of the phospholipase C and phospholipase A2 pathways and the induction of proinflammatory cytokines have been studied in mouse macrophages. 2. Both chloroquine and quinacrine, and to a lesser extent hydroxychloroquine, inhibited arachidonate release and eicosanoid formation induced by phorbol diester. This inhibition was due to that of the activation of the arachidonate-mobilizing phospholipase A2. 3. All three antimalarials potently inhibited arachidonate release induced by zymosan. They also inhibited the zymosan-induced formation of inositol phosphates, which hints that an inhibitory effect at the phospholipase C level might explain the inhibition... (More)
1. The effects of antimalarial drugs on the intracellular signaling leading to activation of the phospholipase C and phospholipase A2 pathways and the induction of proinflammatory cytokines have been studied in mouse macrophages. 2. Both chloroquine and quinacrine, and to a lesser extent hydroxychloroquine, inhibited arachidonate release and eicosanoid formation induced by phorbol diester. This inhibition was due to that of the activation of the arachidonate-mobilizing phospholipase A2. 3. All three antimalarials potently inhibited arachidonate release induced by zymosan. They also inhibited the zymosan-induced formation of inositol phosphates, which hints that an inhibitory effect at the phospholipase C level might explain the inhibition of the response to zymosan. 4. Quinacrine, and to a lesser extent chloroquine, has an inhibitory effect on the lipopolysaccharide- or zymosan-induced expression of interleukin 1beta and tumor necrosis factor alpha, both at the mRNA and protein levels. This, in particular, has important implications for the mode of action of these compounds in rheumatoid arthritis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
General Pharmacology
volume
30
issue
3
pages
66 - 357
publisher
Elsevier
external identifiers
  • scopus:0032033594
ISSN
0306-3623
language
English
LU publication?
yes
id
f1c4a185-e281-48db-960d-0b101677d095 (old id 30118)
date added to LUP
2007-06-19 09:45:44
date last changed
2017-01-01 06:56:02
@article{f1c4a185-e281-48db-960d-0b101677d095,
  abstract     = {1. The effects of antimalarial drugs on the intracellular signaling leading to activation of the phospholipase C and phospholipase A2 pathways and the induction of proinflammatory cytokines have been studied in mouse macrophages. 2. Both chloroquine and quinacrine, and to a lesser extent hydroxychloroquine, inhibited arachidonate release and eicosanoid formation induced by phorbol diester. This inhibition was due to that of the activation of the arachidonate-mobilizing phospholipase A2. 3. All three antimalarials potently inhibited arachidonate release induced by zymosan. They also inhibited the zymosan-induced formation of inositol phosphates, which hints that an inhibitory effect at the phospholipase C level might explain the inhibition of the response to zymosan. 4. Quinacrine, and to a lesser extent chloroquine, has an inhibitory effect on the lipopolysaccharide- or zymosan-induced expression of interleukin 1beta and tumor necrosis factor alpha, both at the mRNA and protein levels. This, in particular, has important implications for the mode of action of these compounds in rheumatoid arthritis.},
  author       = {Bondeson, J and Sundler, Roger},
  issn         = {0306-3623},
  language     = {eng},
  number       = {3},
  pages        = {66--357},
  publisher    = {Elsevier},
  series       = {General Pharmacology},
  title        = {Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages},
  volume       = {30},
  year         = {1998},
}