Kravchenko V V, Steinemann S, Kline L, Feng L, Ulevitch R J
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Shock. 1996 Mar;5(3):194-201. doi: 10.1097/00024382-199603000-00005.
Changes in patterns of gene induction by myeloid lineage cells following multiple exposures to endotoxin (lipopolysaccharide; LPS) is a feature of LPS tolerance. To further understand the mechanism of this phenomenon we describe studies using stably transfected Chinese hamster ovary cell lines that express human CD14 (CHO-hCD14). Using NF-kappa B activation as a measure of LPS-induced cell activation we show that a single treatment with LPS renders CHO-hCD14 cells tolerant to subsequent challenge with LPS, but not with other stimuli such as tumor necrosis factor. Tolerance may result from the induction of gene(s) that control LPS-induced signaling pathways and here we suggest that such genes may be found in the group of immediate, early response genes characterized by the protein phosphatase 3CH134. The CHO-hCD14 cell lines provide a novel model system to further explore the mechanism of endotoxin tolerance.
髓系细胞多次暴露于内毒素(脂多糖;LPS)后基因诱导模式的变化是LPS耐受性的一个特征。为了进一步了解这一现象的机制,我们描述了使用稳定转染的表达人CD14的中国仓鼠卵巢细胞系(CHO-hCD14)进行的研究。以NF-κB激活作为LPS诱导细胞激活的指标,我们发现用LPS单次处理可使CHO-hCD14细胞对随后的LPS刺激产生耐受,但对其他刺激(如肿瘤坏死因子)则无耐受。耐受性可能是由控制LPS诱导信号通路的基因的诱导所致,在此我们认为此类基因可能存在于以蛋白磷酸酶3CH134为特征的即时早期反应基因群体中。CHO-hCD14细胞系为进一步探索内毒素耐受性的机制提供了一个新的模型系统。