HSP70 protects against TNF-induced lethal inflammatory shock.
The heat shock (HS) response is a universal response activated after exposure to various stimuli. The major HS protein (HSP) is the 72 kDa HSP70 with strong homology in different eukaryotic species. We demonstrate that HS treatment of mice leads to a strong induction of HSP70 in several organs and confers significant protection against lethality induced by tumor necrosis factor (TNF). HS prevents high production of interleukin-6 and nitric oxide and reduces severe damage and apoptosis of the enterocytes in the bowel. Mice deficient in the inducible hsp70.1 gene were no longer protected by HS treatment. We show that HS can be applied successfully in an antitumor protocol based on TNF and interferon-gamma, leading to a significant inhibition of lethality but not to a reduction of antitumoral capacity.
Van Molle
Wim
W
Department of Molecular Biology, Unit of Mouse Molecular Genetics, Flanders Interuniversity Institute for Biotechnology and University of Ghent, K.L. Ledeganckstraat 35, 9000 Ghent, Belgium.
Wielockx
Ben
B
Mahieu
Tina
T
Takada
Masuhiro
M
Taniguchi
Takahide
T
Sekikawa
Kenji
K
Libert
Claude
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019610:Cytoprotection; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D018869:Heat-Shock Response; D007035:Hypothermia / Q000378:metabolism / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis; D007421:Intestine, Small / Q000473:pathology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009569:Nitric Oxide / Q000096:biosynthesis; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology; D012769:Shock / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; C081884:heat-shock protein 70.1; D009569:Nitric Oxide; D007371:Interferon-gamma