Cytokine-mediated down-regulation of CYP1A1 in Hepa1 cells.
Cytokine-mediated down-regulation of CYP1A1 in Hepa1 cells.
复制标题
Hepa1 细胞中细胞因子介导的 CYP1A1 下调。
DOI：
10.1016/s0006-2952(98)00028-8
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发表时间：
1998
影响因子：
5.8
通讯作者：
K. Renton
中科院分区：
文献类型：
--
作者：
T. Paton;K. Renton
宿主防御机制的激活下调细胞培养物、人类和动物中的微粒体细胞色素P450。使用体内模型对这种效应的各个方面的研究还没有清楚地定义细胞因子在这种现象中所起的作用。免疫刺激剂，如脂多糖（LPS）的下调机制，探讨了在体外模型，利用鼠肝癌（Hepa 1）和鼠巨噬细胞（IC-21）细胞系。据推测，免疫刺激剂下调P450活性涉及免疫细胞的活化和随后释放细胞因子，如白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）。通过乙氧基试卤灵O-脱烷基酶（一种测量Hepa 1细胞中CYP 1A活性的测定法）评估免疫刺激对P450活性的影响。初步研究表明，LPS直接加入肝癌细胞对CYP 1A 1活性水平没有影响。与此相反，当肝癌细胞与通过将LPS与IC-21细胞一起孵育获得的单核细胞条件培养基一起孵育时，CYP 1A 1活性发生显著下调。当将TNF-α合成抑制剂戊茶碱与LPS共同给予巨噬细胞时，CYP 1A 1活性的下调被阻止。小鼠重组TNF-α直接给药于肝癌细胞导致CYP 1A 1活性下调。这些结果表明，从巨噬细胞释放TNF-α是LPS下调CYP 1A 1的重要步骤。
The activation of host defense mechanisms down-regulates microsomal cytochrome P450 in cell culture, humans, and animals. Investigation into various aspects of this effect using in vivo models has yet to define clearly the role that cytokines play in this phenomenon. The mechanism of down-regulation by immunostimulants, such as lipopolysaccharide (LPS), is explored with an in vitro model, utilizing a murine hepatoma (Hepa1) and a murine macrophage (IC-21) cell line. It is hypothesized that down-regulation of P450 activity by immunostimulants involves the activation of immune cells and the subsequent release of cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The effects of immunostimulation on P450 activity are assessed by ethoxyresorufin O-dealkylase, an assay that measures CYP1A activity in Hepa1 cells. Initial studies demonstrated that LPS added directly to hepatoma cells had no effect on the levels of CYP1A1 activity. In contrast, a significant down-regulation in CYP1A1 activity occurred when hepatoma cells were incubated with monocyte conditioned medium obtained by incubating LPS with IC-21 cells. When pentoxifylline, a TNF-α synthesis inhibitor, was co-administered with LPS to macrophages, the down-regulation of CYP1A1 activity was prevented. The direct administration of murine recombinant TNF-α to hepatoma cells resulted in a down-regulation of CYP1A1 activity. These results implicated the release of TNF-α from macrophages as an important step in the down-regulation of CYP1A1 by LPS.
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内毒素血症和急性期反应期间肝细胞中一氧化氮合酶的差异诱导。
DOI：
10.1001/archsurg.1994.01420260061008
发表时间：
1994
期刊：
Archives of surgery (Chicago, Ill. : 1960)
影响因子：
--
作者：
Geller,DA;Freeswick,PD;Nguyen,D;Nussler,AK;DiSilvio,M;Shapiro,RA;Wang,SC;Simmons,RL;Billiar,TR
通讯作者：
Billiar,TR
在人 HepG2 肝癌细胞中白细胞介素 6 对细胞色素 P450IA1 的抑制。
影响因子：
5.8
作者：
Fukuda,Y;Sassa,S
通讯作者：
Sassa,S
一氧化氮在细胞因子介导的细胞色素 P-450 调节中的作用。
DOI：
--
发表时间：
1996
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Carlson,TJ;Billings,RE
通讯作者：
Billings,RE
DOI：
--
发表时间：
1991-02
期刊：
The American journal of pathology
影响因子：
--
作者：
S. Chensue;D. Pauline;Terebuh;D. Remick;W. Scales;Steven L. Kunkelt
通讯作者：
S. Chensue;D. Pauline;Terebuh;D. Remick;W. Scales;Steven L. Kunkelt
Interleukin-1 beta 抑制分离肝细胞中 P4501A1 和 P4501A2 mRNA 的诱导。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Barker,CW;Fagan,JB;Pasco,DS
通讯作者：
Pasco,DS