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HSP70 protects against TNF-induced lethal inflammatory shock
Wim Van Molle1, Ben Wielockx, Tina Mahieu
1Department of Molecular Biology, Unit of Mouse Molecular Genetics, Flanders Interuniversity Institute for Biotechnology and University of Ghent, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
Immunity
|June 7, 2002
Summary
Heat shock (HS) treatment induces HSP70, protecting mice from lethal tumor necrosis factor (TNF) by reducing inflammation and gut damage. This protective effect relies on the inducible hsp70.1 gene.
Area of Science:
- Cellular biology
- Immunology
- Stress response
Background:
- The heat shock (HS) response is a fundamental cellular defense mechanism against various stressors.
- Heat shock protein 70 (HSP70) is a major component of this response, conserved across eukaryotic species.
- HSP70 plays a critical role in cellular protection and protein homeostasis.
Purpose of the Study:
- To investigate the protective role of HSP70 induction by heat shock against lethal tumor necrosis factor (TNF) challenge.
- To elucidate the mechanisms underlying HSP70-mediated protection, including effects on inflammatory mediators and tissue damage.
- To evaluate the efficacy of HS treatment in combination with an antitumor protocol.
Main Methods:
- Mice were subjected to heat shock (HS) treatment.
- HSP70 expression levels were assessed in various organs.
- Mice were challenged with lethal doses of TNF.
- Levels of interleukin-6 (IL-6) and nitric oxide (NO) were measured.
- Intestinal enterocyte damage and apoptosis were evaluated.
- Experiments were conducted using wild-type and hsp70.1 gene-deficient mice.
- HS treatment was integrated into an antitumor protocol involving TNF and interferon-gamma (IFN-γ).
Main Results:
- HS treatment significantly increased HSP70 levels in multiple organs.
- HS conferred significant protection against TNF-induced lethality.
- HS treatment reduced high production of IL-6 and NO.
- HS mitigated severe damage and apoptosis in intestinal enterocytes.
- Mice lacking the inducible hsp70.1 gene did not exhibit HS-induced protection.
- Combined HS and antitumor therapy (TNF + IFN-γ) reduced lethality but did not impair antitumor capacity.
Conclusions:
- HSP70 induction via heat shock provides substantial protection against TNF-induced mortality.
- The protective effects are mediated by the suppression of key inflammatory molecules and the preservation of intestinal integrity.
- The inducible hsp70.1 gene is essential for HS-induced protection.
- Heat shock can be a valuable adjunct therapy in cancer treatment protocols involving TNF and IFN-γ, enhancing survival without compromising efficacy.