Warming macrophages to febrile range destabilizes tumor necrosis factor-alpha mRNA without inducing heat shock
| Autor: | Eric K. Crawford, Jeffrey D. Hasday, J. E. Ensor |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Hot Temperature
Fever Transcription Genetic Lipopolysaccharide Physiology MRNA destabilization medicine.medical_treatment Biology Cell Line Mice chemistry.chemical_compound Polysome medicine Animals RNA Messenger Heat shock Interleukin-6 Tumor Necrosis Factor-alpha Macrophages Monocyte Shock Cell Biology Molecular biology Cytokine medicine.anatomical_structure chemistry Cell culture Polyribosomes Protein Biosynthesis Immunology Tumor necrosis factor alpha Half-Life |
| Zdroj: | American Journal of Physiology-Cell Physiology. 269:C1140-C1146 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1995.269.5.c1140 |
| Popis: | We have previously reported that sustained tumor necrosis factor (TNF)-alpha expression is suppressed by temperatures in the febrile range in human macrophages. In this study, we examined the mechanisms of high-temperature-induced macrophage TNF suppression in the RAW 264.7 macrophage cell line. Incubating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells at 40 degrees C reduced TNF secretion by 92% and peak TNF mRNA levels by 43% compared with cells incubated at 37 degrees C (P < 0.05) but did not affect levels of glyceraldehyde-3-phosphate dehydrogenase, beta-actin, or interleukin-6 mRNA. TNF mRNA half-life, measured after transcriptional arrest with actinomycin D, was reduced from 21.8 +/- 3.6 min in LPS-stimulated RAW 264.7 cells at 37 degrees C to 16.0 +/- 1.8 min at 40 degrees C (P < 0.03), but these cells at 40 degrees C did not alter transcription rate or TNF mRNA polysome association. TNF mRNA destabilization occurred at temperatures below the threshold (43 degrees C) for the generalized heat shock response in these cells. We conclude that heating macrophages to febrile-range temperatures attenuates sustained TNF expression by modulating posttranscriptional processing, including acceleration of TNF mRNA decay. |
| Databáze: | OpenAIRE |
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