Gelatinase B deficiency protects against endotoxin shock

Dubois, Bénédicte; Starckx, Sofie; Pagenstecher, Axel; Oord, Joost van den; Arnold, Bernd; Opdenakker, Ghislain

doi:10.1002/1521-4141(200208)32:8<2163::aid-immu2163>3.0.co;2-q

Cited by 81 publications

(45 citation statements)

References 40 publications

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“…These differences, which have been observed in other studies (28), could be responsible for the benefits of lacking MMP-9 in other models of injury (12). Together, these results suggest a translocation of the inflammatory response to the alveolar space in knockout animals ventilated with high pressure, in spite of decreased levels of cytokines in basal conditions (low pressure ventilation).…”

Section: Discussionsupporting

confidence: 62%

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Albaiceta¹,

Gutiérrez‐Fernández²,

Parra³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionsupporting

confidence: 62%

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Albaiceta¹,

Gutiérrez‐Fernández²,

Parra³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…During local and systemic bacterial infections, inflammatory responses play a very important role in fighting the pathogens, but, in contrast, can also cause tissue damage. Previously, it was demonstrated that MMP-9 deficiency protects against mortality in an endotoxic shock model in mice, and selective MMP-9 blocking was suggested as a possible new therapeutic approach for sepsis (9). However, although this study clearly established the anti-inflammatory potential of MMP-9 inhibition, the endotoxin model does not adequately mimic clinical sepsis because it lacks an infectious source from which bacteria invade the host and cause a systemic inflammatory response syndrome.…”

Section: Discussionmentioning

confidence: 84%

“…LPS, the major constituent of the outer cell wall of Gram-negative bacteria and the principal mediator of inflammatory responses to these pathogens, induces the release of MMP-9 by neutrophils and monocytes in vitro (7,8). Moreover, in mice, E. coli LPS administration led to a quick release of MMP-9 into the circulation, with peak values as soon as 1 h after injection (9). In line, during experimental endotoxemia in healthy human volunteers, plasma levels of MMP-9 increased strongly, peaking at 1.5-3 h after LPS injection (10).…”

mentioning

confidence: 66%

Matrix Metalloproteinase-9 Deficiency Impairs Host Defense against Abdominal Sepsis

Renckens¹,

Roelofs²,

Florquin³

et al. 2006

The Journal of Immunology

109

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Matrix metalloproteinase (MMP)-9 is involved in extracellular matrix degradation and leukocyte migration. To determine the role of MMP-9 in the innate immune response to peritonitis, MMP-9 gene-deficient (MMP-9−/−) and normal wild-type mice were i.p. infected with Escherichia coli. MMP-9 mRNA and pro-MMP-9 protein levels increased rapidly upon induction of peritonitis. Although MMP-9−/− neutrophils showed a normal phagocytosis of E. coli in vitro, MMP-9−/− mice displayed a reduced resistance against E. coli peritonitis, as indicated by an enhanced bacterial outgrowth in the peritoneal cavity and increased dissemination of the infection. Furthermore, the cytokine response to LPS was not influenced by MMP-9 deficiency. However, during E. coli peritonitis, MMP-9−/− mice showed much higher peritoneal chemokine and cytokine levels compared with wild-type mice. Despite the increased local chemokine concentrations, MMP-9−/− mice displayed a diminished recruitment of leukocytes to the site of infection, indicating that cellular migration was impaired. Moreover, MMP-9−/− mice developed more severe distant organ damage during infection. These data suggest that MMP-9 is an essential component of an effective host response to E. coli peritonitis.

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“…Activated MMPs trigger the degradation of ECM components such as collagens, gelatin, and fibronectin. MMP-9 (gelatinases B) expression is induced by proinflammatory stimuli including cytokines, chemokines, and bacterial wall components [25,26], and data suggest a role for MMPs, especially MMP-9, in the development of NASH. Steatohepatitis may lead to hepatic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Glutathione‐enhancing agents protect against steatohepatitis in a dietary model

Chen

et al. 2006

J Biochem & Molecular Tox

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Nonalcoholic fatty liver (NAFL) and steatohepatitis (NASH) may accompany obesity, diabetes, parenteral nutrition, jejeuno-ileal bypass, and chronic inflammatory bowel disease. Currently there is no FDA approved and effective therapy available. We investigated the potential efficacy of those agents that stimulate glutathione (GSH) biosynthesis on the development of experimental steatohepatitis. Rats fed (ad libitum) amino acid based methionine-choline deficient (MCD) diet were further gavaged with (1) vehicle (MCD), (2) S-adenosylmethionine (SAMe), or (3) 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA). Results: MCD diet significantly reduced hematocrit, and this abnormality improved in the treated groups ( p < 0.01). Serum transaminases were considerably elevated (AST: 5.8-fold; ALT: 3.22-fold) in MCD rats. However, administration of GSH-enhancing agents significantly suppressed these abnormal enzyme activities. MCD rats developed severe liver pathology manifested by fatty degeneration, inflammation, and necrosis, which significantly improved with therapy. Blood levels of GSH were significantly depleted in MCD rats but normalized in the treated groups. Finally, RT-PCR measurements showed a significant upregulation of genes involved in tissue remodeling and fibrosis (matrix metalloproteinases, collagen-␣1), suppressor of cytokines signaling1, and the inflammatory cytokines (IL-1␤, IL-6, TNF-␣, and TGF-␤) in the livers of rats fed MCD. GSH-enhancing therapies significantly attenuated the expression of deleterious proinflammatory and fibrogenic genes in this dietary model. This is the first report that oral administration of SAMe and PTCA provide protection against liver injury in this model and suggests therapeutic applications of these compounds in NASH patients. C

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Gelatinase B deficiency protects against endotoxin shock

Cited by 81 publications

References 40 publications

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

Matrix Metalloproteinase-9 Deficiency Impairs Host Defense against Abdominal Sepsis

Glutathione‐enhancing agents protect against steatohepatitis in a dietary model

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