文章基本信息

标题：Structure-Activity Relationships of Lipopolysaccharide (LPS) in Tumor Necrosis Factor-α (TNF-α) Production and Induction of Macrophage Cell Death in the Presence of Cycloheximide (CHX) in a Murine MacrophageLike Cell Line, J774.1
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作者：Hisae KARAHASHI ; Fumio AMANO
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：10
页码：1102-1105
DOI：10.1248/bpb.21.1102
出版社：The Pharmaceutical Society of Japan
摘要：The structure-activity relationships of lipopolysaccharide (LPS) in tumor necrosis factor-α (TNF-α) production and induction of macrophage cell death in the presence of cycloheximide (CHX) were examined in a murine macrophage-like cell line, J774.1. TNF-α production is one of the characteristic phenotypes of LPS-activated macrophages, and is observed upon incubation with LPS. On the contrary, macrophage cell death, which had been found in our laboratory (Amano F., Karahashi H., J. Endotoxin Res., 3, 415-423 (1996)) and was examined as the release of lactate dehydrogenase (LDH) from cells into the culture supernatant, was observed 2.5 h after the addition of LPS in the presence of CHX. However, both TNF-α production and macrophage cell death were similarly dependent on the structures of LPS and lipid A. At more than 10 ng/ml, wild-type LPS from E.coli and S. minnesota exhibited the highest activity, and LPS as well as diphosphoryl lipid A from S. minnesota rough mutants also exhibited activity, but E. coli LPS detoxified by alkaline treatment or monophosphoryl lipid A from S. minnesota exhibited no activity even at 100 ng/ml. These results suggest that LPS-induced macrophage cell death in the presence of CHX shows similar requirements for LPS and/or lipid A structures as for the macrophage activation at higher doses than 10 ng/ml, although the former was not observed at 1 ng/ml LPS, while the latter was. However, TNF-α does not seem to be involved in the induction of macrophage cell death, because a neutralizing anti-TNF-α antibody failed to block the macrophage cell death and because recombinant TNF-α had little effect on the extent of LDH release in the presence or absence of LPS and/or CHX, and also because TNF-αproduction by LPS was abolished in the presence of CHX.
关键词：cell death;J774.1;lipid A;lipopolysaccharide (LPS);macrophage;tumor necrosis factor-α (TNF-α)