Endotoxin tolerance is induced in Chinese hamster ovary cell lines expressing human CD14.
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.
Kravchenko
V V
VV
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Steinemann
S
S
Kline
L
L
Feng
L
L
Ulevitch
R J
RJ
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D004361:Drug Tolerance; D005069:Evaluation Studies as Topic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha