Selective inhibition of human glial inducible nitric oxide synthase by interferon-beta: implications for multiple sclerosis.
Nitric oxide generated from the inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of multiple sclerosis. Because significant species- and cell-specific differences exist in the expression of iNOS, we used primary human glial cell cultures to screen for an inhibitor of iNOS expression. Remarkably, among numerous soluble factors tested, interferon-beta (IFN-beta) alone showed a selective and potent inhibition of interleukin-1beta/interferon-gamma (IL-1beta/IFN-gamma)-induced iNOS expression in astrocytes. Inhibition of iNOS may provide a mechanism by which IFN-beta can ameliorate inflammation and cytotoxicity in the central nervous system of patients with multiple sclerosis.
Hua
L L
LL
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Liu
J S
JS
Brosnan
C F
CF
Lee
S C
SC
D001253:Astrocytes / Q000201:enzymology*; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000502:physiology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D009103:Multiple Sclerosis / Q000201:enzymology / Q000628:therapy; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II
D016899:Interferon-beta; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II