Biomedical subjects

Claude Libert

Publications and source records attributed to Claude Libert.

22 records · Page 2Linked to original sources

PubMed2002

Hyporesponsiveness of SPRET/Ei mice to lethal shock induced by tumor necrosis factor and implications for a TNF-based antitumor therapy.

Tumor necrosis factor (TNF) is a central mediator in lethal shock and an interesting cytokine for anticancer therapy. To inhibit TNF-induced lethal shock, it is important to identify protective genes. Here we demonstrate that the SPRET/Ei mouse strain, derived from Mus spretus, exhibits an extremely dominant resistance to TNF-induced lethal inflammation. An interspecific backcross experiment revealed that the TNF hyporesponse is linked to loci on chromosomes 2, 6, and 11. Treatment of inoculated tumors with TNF and IFN-gamma leads to regression and a highly reduced toxicity in (C57BL/6 x SPRET/Ei)F(1) mice.

Animals↗

PubMed2002

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.

Animals↗

PubMedDate not supplied

Matrilysin (matrix metalloproteinase-7): a new promising drug target in cancer and inflammation?

Matrilysin or MMP-7, one of the smallest of all known matrix metalloproteinases (MMPs), has been studied extensively in many different tumor types, since its discovery more than 20 years ago. However, research during the past several years has revealed that this protease also plays an essential role in innate immunity, and, more particularly, in inflammatory disorders.

Animals↗

PubMedDate not supplied

Mice lacking alpha(2)-macroglobulin show an increased host defense against Gram-negative bacterial sepsis, but are more susceptible to endotoxic shock.

The onset of an acute phase response is one of the initial steps in the defense against an infectious organism. Alpha(2)-macroglobulin (alpha(2)M), an acute phase protein in most mammalian species, is known to have a broad antiprotease activity, but it can also bind a number of growth factors, cytokines, ions and lipid factors. We have shown that alpha(2)M-deficient (MAM-/-) mice are more resistant to a lethal Gram-negative infection compared to control mice. This increased resistance was reflected in significantly higher body temperatures, compared to control mice, during the infection as well as in a prolonged and increased survival. Moreover, the clearance of bacteria in MAM-/- mice was significantly more efficient than in control mice. On the other hand, MAM-/- mice were more susceptible to endotoxin. An LD(100) challenge with endotoxin in MAM-/- mice was not lethal for control mice. Our data suggest that alpha(2)M plays a dual role during an acute phase response. In the establishment of a lethal Gram-negative infection, leading to sepsis and septic shock, it has a mediating role by hampering the efficient clearance of bacteria. During endotoxic shock, however, alpha(2)M has a rather protective function.

Animals↗