Warming macrophages to the febrile range destabilizes tumor
necrosis factor-[alpha] mrna without inducing heat-shock.
Ensor, Jeffery E., Eric K. Crawford, and Jeffrey D. Hasday.
Division of Pulmonary and Critical Care Medicine, Departments of
Medicine and Pathology, University of Maryland School of Medicine,
Baltimore, MD 21201 and the Medical Research Service of the Baltimore
Veterans Administration Medical Center, Baltimore, MD 21201
APStracts 2:0218C, 1995.
We have previously reported that sustained tumor necrosis factor
-[alpha] (TNF) 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 C reduced TNF secretion by 92% and
peak TNF mRNA levels by 43% compared with cells incubated at 37 (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 minutes in LPS- stimulated Raw 264.7 cells at
37 C to 16.0+/-1.8 minutes at 40 C (p < 0.03), but these cells at 40
C did not alter transcription rate or TNF mRNA polysome association.
TNF mRNA destabilization occurred at temperatures below the threshold
(43 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.
Received 24 February 1995; accepted in final form 15 May 1995.
APS Manuscript Number C105-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.