Decreased acid-labile subunit (ALS) levels by endotoxin in vivo and by interleukin-1β in vitro

被引:26
作者
Barreca, A
Ketelslegers, JM
Arvigo, M
Minuto, F
Thissen, JP
机构
[1] Univ Genoa, Dept Endocrinol & Metab, I-16132 Genoa, Italy
[2] Univ Louvain, Diabet & Nutr Unit, B-1200 Brussels, Belgium
关键词
acid-labile subunit; ALS; rat liver; hepatocytes; growth hormone; endotoxin; cytokines;
D O I
10.1016/S1096-6374(98)80114-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The production by the liver of the three subunits of the growth hormone (GH)-dependent 150 kDa complex (IGF-I, IGF-binding protein-3 and acid-labile subunit or ALS) is primarily under the control of GH. Recent data have shown that, besides GH, endotoxin (LPS) and cytokines may regulate the liver IGF-I gene. To investigate the potential regulation of ALS by LPS, we measured serum ALS by immunoblot, 5 and 10 h after IP injection of LPS (250 or 750 mu g/100 g BW vs saline), in 4-week-old female Wistar rats (four per group). Ten hours after injection, serum ALS levels were reduced by 57% (Delta%) with the lower dose (P<0.05) and by 81% with the higher dose (P<0.01) by comparison with saline-treated rats. The decrease in ALS levels in response to LPS was not prevented by exogenous GH. To investigate the role of interleukin (IL)-1 beta in the regulation of ALS, primary cultured rat hepatocytes were exposed to increasing concentrations of IL-1 beta. Cell exposure to IL-1 beta markedly decreased both basal and GH-stimulated ALS levels (-70%, P<0.01) in a dose-dependent fashion, with the half-maximal inhibitory effect at concentrations of 0.1 ng/ml. Our results show that endotoxin induces a rapid decline in circulating ALS that is potentially mediated through IL-1 beta. By limiting the formation of the 150 kDa complex, this reduction in circulating ALS might contribute to the rapid decline in serum IGF-I observed in sepsis. (C) 1998 Churchill Livingstone.
引用
收藏
页码:217 / 223
页数:7
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