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Chonnam Med J. 2000 Jun;36(2):209-218. Korean. Original Article.
Chung SY , Choi SJ , Kim SK , So HS , Jung BH , Song HS , Kim MS , Park JS , Chae KM , Lee JH , Che HJ , Kim HR , Chung HT , Park R .
Department of Microbiology, Wonkwang University School of Medicine, Iksan, Chonbuk.
Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Chonbuk.
Department of Surgery, Wonkwang University School of Medicine, Iksan, Chonbuk.
Department of Microbiology, Chonbuk National University Medical School, Chonju, Chonbuk.
Department of Surgery, Chonnam National University Medical School Kwangju.
Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Korea.
Abstract

Although it has been well known that the role of LPS on liver damage 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 treatment of LPS (0.5 ug/ml). In addition, over 25 uM of sodium nitroprusside (SNP), an exogenous NO donor, significantly prevents cell death by IFN-gamma alone or IFN-gamma plus LPS (IFN-gamma/LPS) in a dose-dependent manner. In addition, SNP efficiently blocked death of BNL-CL2 cells only when it was added within 12 hr after treatment of IFN-gamma and IFN-gamma/LPS. However, potassium ferrocyanide (PFC), a structural analog of SNP, did not show any protective effect on the IFN-gamma alone or IFN-gamma/LPS-induced BNL-CL2 cell death. The preventive effect of SNP occurs in parallel with the suppression of caspase 3-like protease activation. In addition, we have demonstrated that a relatively high concentration as well as an appropriate period of exposure to NO may be critical to maintain cell viability against cytotoxicity by IFN-gamma and IFN-gamma LPS. Furthermore, the preventive effect of SNP in IFN-gamma/LPS-induced cell death is mediated by a protein kinase G (PKG)-independent manner.

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