Warming macrophages to febrile range destabilizes tumor necrosis factor-alpha mRNA without inducing heat shock

Ensor, J. E.; Crawford, Eric K.; Hasday, Jeffrey D.

doi:10.1152/ajpcell.1995.269.5.c1140

Cited by 52 publications

(50 citation statements)

References 19 publications

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“…These data suggest that febrile core temperature is predominantly suppressive for TNF-␣ expression during bacterial infections. This finding in the febrile animals is consistent with the early deactivation of TNF-␣ gene expression in macrophages in vitro previously reported by our laboratory (11,12,18), an effect caused by destabilization of TNF-␣ mRNA (11), and an early cessation of transcription (21a). The latter effect is mediated in part by partial activation of heat shock factor 1.…”

Section: Discussionsupporting

confidence: 91%

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Febrile Core Temperature Is Essential for Optimal Host Defense in Bacterial Peritonitis

et al. 2000

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Fever, a nonspecific acute-phase response, has been associated with improved survival and shortened disease duration in infections, but the mechanisms of these beneficial responses are poorly understood. We previously reported that increasing core temperature of bacterial endotoxin (LPS)-challenged mice to the normal febrile range modified expression of tumor necrosis factor alpha (TNF-␣), interleukin 1␤ (IL-1␤), and IL-6, three cytokines critical to mounting an initial defense against microbial pathogens, but survival was not improved in the warmer animals. We speculated that our inability to show a survival benefit of optimized cytokine expression in the warmer animals reflected our use of LPS, a nonreplicating agonist, rather than an infection with viable pathogens. The objective of this study was to determine if increasing murine core temperature altered cytokine expression and improved survival in an experimental bacterial peritonitis model. We showed that housing mice at 35.5°C rather than 23°C increased core temperature from 36.5 to 37.5°C to 39.2 to 39.7°C, suppressed plasma TNF-␣ expression for the initial 48 h, delayed gamma interferon expression, improved survival, and reduced the bacterial load in mice infected with Klebsiella pneumoniae peritonitis. We showed that the reduced bacterial load was not caused by a direct effect on bacterial proliferation and probably reflected enhanced host defense. These data suggest that the increase in core temperature that occurs during bacterial infections is essential for optimal antimicrobial host defense.

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Section: Discussionsupporting

confidence: 91%

“…Mean Ϯ SE; n ϭ 6; ‫,ء‬ P Ͻ 0.05 compared with the "no fever" mice. (11,12,18). We also reported that increasing core temperature in LPS-challenged mice accelerated and enhanced an early, self-limited pulse of TNF-␣ in plasma but subsequently suppressed persistent TNF-␣ expression and enhanced the expression of IL-6 (17,18).…”

Section: Resultsmentioning

confidence: 99%

Febrile Core Temperature Is Essential for Optimal Host Defense in Bacterial Peritonitis

et al. 2000

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“…We showed that exposing RAW cells to 39.5°C for 2-4 h increased Hsp70 mRNA levels 7-15-fold. In an earlier study, we found that exposing RAW cells to 40°C failed to activated Hsp70 mRNA expression (45), but the cells were only heated for 30 min in the previous study. The results of the two studies are consistent with our observation that Hsp70 induction at less extreme hyperthermia requires longer exposure time (27).…”

Section: Discussionmentioning

confidence: 77%

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

Gupta¹,

Cooper²,

Tulapurkar³

et al. 2013

Journal of Biological Chemistry

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“…This suggests that macrophages and/or neutrophils are the critical cell type that must regulate TNF-␣ production during a fever response in order to prevent septic shock. In fact, the Hasday group showed that transcription of TNF-␣ was inhibited in a variety of different monocyte and macrophage cell types exposed to physiologic fever temperature (39.5°C) and that this transcriptional regulation was dependent on HSF1 (9,10,37).…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Factor 1 Protects Mice from Rapid Death duringListeria monocytogenesInfection by Regulating Expression of Tumor Necrosis Factor Alpha during Fever

et al. 2011

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Heat shock factor 1 (HSF1) is a stress-induced transcription factor that promotes expression of genes that protect mammalian cells from the lethal effects of severely elevated temperatures (>42°C). However, we recently showed that HSF1 is activated at a lower temperature (39.5°C) in T cells, suggesting that HSF1 may be important for preserving T cell function during pathogen-induced fever responses. To test this, we examined the role of HSF1 in clearance of Listeria monocytogenes, an intracellular bacterial pathogen that elicits a strong CD8؉ T cell response in mice. Using temperature transponder microchips, we showed that the core body temperature increased approximately 2°C in L. monocytogenes-infected mice and that the fever response was maintained for at least 24 h. HSF1-deficient mice cleared a low-dose infection with slightly slower kinetics than did HSF1 ؉/؉ littermate controls but were significantly more susceptible to challenges with higher doses of bacteria. Surprisingly, HSF1-deficient mice did not show a defect in CD8 ؉ T cell responses following sublethal infection. However, when HSF1-deficient mice were challenged with high doses of L. monocytogenes, increased levels of serum tumor necrosis factor alpha (TNF-␣) and gamma interferon (IFN-␥) compared to those of littermate control mice were observed, and rapid death of the animals occurred within 48 to 60 h of infection. Neutralization of TNF-␣ enhanced the survival of HSF1-deficient mice. These results suggest that HSF1 is needed to prevent the overproduction of proinflammatory cytokines and subsequent death due to septic shock that can result following high-dose challenge with bacterial pathogens.

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Warming macrophages to febrile range destabilizes tumor necrosis factor-alpha mRNA without inducing heat shock

Cited by 52 publications

References 19 publications

Febrile Core Temperature Is Essential for Optimal Host Defense in Bacterial Peritonitis

Febrile Core Temperature Is Essential for Optimal Host Defense in Bacterial Peritonitis

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

Heat Shock Factor 1 Protects Mice from Rapid Death duringListeria monocytogenesInfection by Regulating Expression of Tumor Necrosis Factor Alpha during Fever

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