Differential regulation of nitric oxide synthase mRNA expression by lipopolysaccharide and pro-inflammatory cytokines in fetal hepatocytes treated with cycloheximide

被引:8
作者
Casado, M [1 ]
DiazGuerra, MJM [1 ]
Bosca, L [1 ]
MartinSanz, P [1 ]
机构
[1] UNIV COMPLUTENSE MADRID,FAC FARM,CSIC,INST BIOQUIM,E-28040 MADRID,SPAIN
关键词
D O I
10.1042/bj3270819
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effect of cycloheximide (CHX) on the mRNA expression of the cytokine-inducible, calcium-independent nitric oxide synthase (iNOS) was investigated in fetal hepatocytes stimulated with lipopolysaccharide (LPS) or pro-inflammatory cytokines. In the presence of CHX the LPS-dependent iNOS mRNA levels were reduced, whereas the response to pro-inflammatory cytokines was enhanced, Because iNOS transcription is highly dependent on the activation of nuclear factor kappa B (NF-kappa B), this factor was evaluated by electrophoretic mobility shift assays, and a close correlation between NF-kappa B activity and iNOS mRNA levels was observed. CHX itself potentiated the degradation of the I kappa B alpha and I kappa B beta inhibitory subunits (I kappa B is inhibitory kappa B) of the NF-kappa B complex, and therefore the loss of LPS-dependent iNOS mRNA expression cannot be attributed to a blockage in the activation of NF-kappa B. These results suggest the existence of a CHX-sensitive pathway in the expression of iNOS mediated by LPS, a mechanism that is not involved in the response to pro-inflammatory cytokines.
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收藏
页码:819 / 823
页数:5
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