Differential regulation by cytokines of human astrocyte nitric oxide production.
Reactive nitrogen intermediates, such as nitric oxide (NO), play an important role in host-defense and injury. Human astrocytes released abundant NO upon stimulation with the pro-inflammatory cytokine interleukin (IL)-1 beta, which was potentiated by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. IL-1 receptor antagonist protein markedly attenuated astrocyte NO production. The anti-inflammatory cytokines IL-4 and IL-10 potently suppressed IL-1 beta plus IFN-gamma-stimulated NO, while transforming growth factor-beta preferentially inhibited IL-1 beta plus TNF-alpha-stimulated production of NO. These findings suggest that while IL-1 plays a key role in inducing astrocyte NO production, anti-inflammatory cytokines have the capacity to downregulate NO production by IL-1-stimulated astrocytes.
Hu
S
S
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, Minnesota 55404, USA.
Sheng
W S
WS
Peterson
P K
PK
Chao
C C
CC
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005333:Fetus; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*
D016207:Cytokines; D009569:Nitric Oxide