Nitric oxide prevents the IFN-gamma/LPS-induced hepatotoxicity in a protein kinase G-independent manner.
Although it has been well known that the role of LPS on hepatotoxicity is mediated through TNF-alpha, the direct cytotoxic effect of LPS on IFN-gamma-primed hepatocytes has not yet been clearly demonstrated. Here, we demonstrate that the IFN-gamma-mediated death of murine embryonic liver BNL CL2 cells is potentiated by LPS (0.5 microg/ml). In addition, an exogenous NO donor, sodium nitroprusside (SNP) significantly prevents cell death induced by IFN-gamma alone or IFN-gamma plus LPS (IFN-gamma/LPS) in a dose-dependent manner over 25 microM. SNP significantly blocked the death of BNL CL2 cells only when it was added within 12 hr after treatment of IFN-gamma and IFN-gamma/LPS. The preventive effect of SNP occurred in parallel with the suppression of caspase 3-like protease activation. We have also demonstrated that a relatively high concentration as well as an appropriate period of exposure to NO may be critical to maintain cell viability from the cytotoxic effect of IFN-gamma and IFN-gamma/LPS. Furthermore, the preventive effect of SNP on IFN-gamma/LPS-induced cell death is mediated by a protein kinase G (PKG)-independent manner.
So
H S
HS
Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, Korea.
Jung
B H
BH
Song
H S
HS
Myung
Kim
S
S
Park
J S
JS
Chae
K M
KM
Lee
J H
JH
Chung
S Y
SY
Chae
H J
HJ
Kim
H R
HR
Park
R
R
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007371:Interferon-gamma / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011994:Recombinant Proteins
D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D011994:Recombinant Proteins; D009599:Nitroprusside; D009569:Nitric Oxide; D007371:Interferon-gamma; D017869:Cyclic GMP-Dependent Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D006152:Cyclic GMP