The involvement of an LPS inducible I kappa B kinase in endotoxin tolerance
The involvement of an LPS inducible I kappa B kinase in endotoxin tolerance
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DOI：
10.1006/bbrc.1997.6337
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发表时间：
1997-03-27
影响因子：
3.1
通讯作者：
Joly, A
中科院分区：
文献类型：
--
作者：
Kohler, NG;Joly, A
当人卵巢癌细胞受到内毒素攻击时，在3到5分钟内瞬时诱导了一种I kappa B激酶。这种酶的活性导致I kappa B的过度磷酸化和随后的降解，这使得NF-kappa B转位到细胞核，在那里它激活了转录。当内毒素处理的细胞再用第二次内毒素攻击时，未检测到I kappa B激酶，而I kappa B仍留在其隔离核因子kappaB的细胞质中。本文报道了内毒素耐受细胞中缺乏内毒素诱导的I kappa B激酶活性，提示I kappa B激酶可能在内毒素耐受中发挥重要作用。当对内毒素耐受的细胞用肿瘤坏死因子处理时，I-kappa B激酶活性被诱导。因此，对内毒素耐受的细胞对肿瘤坏死因子不具有交叉耐受性。地塞米松是一种已知的核因子-kappaB激活的抑制剂，但不能抑制内毒素依赖的I kappa B激酶的诱导，提示地塞米松的作用机制与本文报道的耐受机制不同。(C)1997年学术出版社。
When human ovarian carcinoma cells are challenged with endotoxin, an I kappa B kinase is transiently induced within 3 to 5 min. This enzyme activity causes the hyperphosphorylation and subsequent degradation of I kappa B which allows NF-kappa B to translocate to the nucleus where it activates transcription. When endotoxin treated cells are rechallenged with a second dose of LPS, I kappa B kinase is not detected and I kappa B remains in the cytoplasm where it sequesters NF-kappa B. We report here the absence of endotoxin inducible I kappa B kinase activity in endotoxin tolerant cells suggesting that I kappa B kinase may play an important role in endotoxin tolerance. When cells tolerant to endotoxin are treated with TNF, I kappa B kinase activity is induced. Thus cells that are endotoxin tolerant are not cross tolerant to TNF. Dexamethasone, a known inhibitor of NF-kappa B activation does not inhibit endotoxin dependent induction of I kappa B kinase suggesting that the mechanism of action of dexamethasone is different from the tolerance mechanism reported here. (C) 1997 Academic Press.