A labile transcriptional repressor modulates endotoxin tolerance
| Autor: | K. E. A. Larue, C. E. Mccall |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Lipopolysaccharides
Transcription Genetic Lipopolysaccharide Emetine Immunology Repressor Biology Cell Line chemistry.chemical_compound Drug tolerance Transcription (biology) Gene expression Tumor Cells Cultured Protein biosynthesis Humans Immunology and Allergy RNA Messenger Cycloheximide Transcription factor Cell Nucleus Dose-Response Relationship Drug Interleukin Articles Drug Tolerance Blotting Northern Molecular biology Repressor Proteins Kinetics chemistry Tetradecanoylphorbol Acetate Puromycin Interleukin-1 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.180.6.2269 |
| Popis: | Tolerance to bacterial lipopolysaccharide (LPS, endotoxin) is an adaptive cellular process whereby exposure to endotoxin induces a subsequent hyporesponsive state characterized by decreased levels of LPS-induced cytokine mRNA and protein. We demonstrate, in a human promonocytic cell line, THP-1, that endotoxin tolerance is manifested by decreased LPS-induced interleukin 1 beta (IL-1 beta) transcription. Inhibition of protein synthesis reverses the tolerant phenotype by inducing transcription of IL-1 beta in the absence of a second stimulus. These results indicate that a labile protein contributes to the endotoxin-tolerant phenotype, and that this factor acts in a dominant repressive manner to inhibit the activity of existing transcription factors. We provide further data that cellular expression of I kappa B-alpha correlates with downregulated IL-1 beta gene expression during endotoxin tolerance, implicating I kappa B-alpha as a potential candidate for the labile repressor identified herein. |
| Databáze: | OpenAIRE |
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