title: Inhibition of neutrophil collagenase/MMP-8 and gelatinase B/MMP-9 and protection against endotoxin shock.
abstract: Endotoxin shock is a life-threatening disorder, associated with the rapid release of neutrophil enzymes, including neutrophil collagenase/matrix metalloproteinase-8 (MMP-8) and gelatinase B/matrix metalloproteinase-9 (MMP-9). After activation, these enzymes cleave extracellular matrix components and cytokines and thus may contribute to shock syndrome development. MMP inhibitors have been suggested as immunotherapy of endotoxin shock. However, little is known about the therapeutic time window of MMP inhibition. Here, a sublethal endotoxin shock mouse model was used to evaluate the effect of an MMP inhibiting peptide (P2) after intravenous or intraperitoneal injection and to study the time window between LPS and inhibitor injections. With the use of a specific ELISA the plasma P2 concentrations were monitored. Whereas we corroborated the treatment strategy of MMP targeting in endotoxin shock with a new inhibitor, we also demonstrated that the time window, within which effective MMP inhibition increased the survival rates, is rather limited.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Hand Surgery, Union Hospital of Tongji Medical College, Wuhan 430022, China.
authors.forename: Jianghai
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hanmei
authors.initials: H
authors.lastname: Xu
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Van den Steen
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jialiang
authors.identifier: 0000-0002-6630-1514
authors.initials: J
authors.lastname: Hu
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000276:immunology; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D012772:Shock, Septic / Q000276:immunology / Q000517:prevention & control*
chemical_list: D008070:Lipopolysaccharides; D010446:Peptide Fragments; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9