| Transglutaminase type II is involved in the pathogenesis of endotoxic shock. | |
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MedLine Citation:
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PMID: 18250473 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The pathogenesis of sepsis is characterized by the inability of the host to regulate the inflammatory response, and as a consequence, dysregulated inflammatory processes induce organ dysfunctions and death. Altered transglutaminase type II (TG2) expression is associated with the development of many inflammatory diseases. Therefore, in this study, we questioned whether TG2 could also contribute to the pathological inflammatory dysregulation occurring in septic shock in vivo. To this aim, we used as an experimental model the TG2 knockout mice, in which the process of septic shock was elicited by treatment with LPS. Interestingly, our results demonstrated that TG2 ablation leads to partial resistance to experimental sepsis. The increased survival of TG2(-/-) mice was reflected in a drastic reduction of organ injury, highlighted by a limited infiltration of neutrophils in kidney and peritoneum and by a better homeostasis of the proinflammatory mediators as well as mitochondrial function. We also showed that in wild-type mice, the TG2 expression is increased during endotoxemia and, being directly involved in the mechanisms of NF-kappaB activation, it may cause a continuous activation cycle in the inflammatory process, thus contributing to development of sepsis pathogenesis. We propose that the inhibition of TG2 could represent a novel approach in the treatment of inflammatory processes associated with sepsis. |
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Authors:
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Laura Falasca; Maria Grazia Farrace; Alessandra Rinaldi; Loretta Tuosto; Gennard Melino; Mauro Piacentini |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 180 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-05 Completed Date: 2008-04-17 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2616-24 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Electron Microscopy, National Institute for Infectious Diseases L. Spallanzani, Rome, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Kidney Injury
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enzymology,
pathology Animals Endotoxemia / enzymology, etiology, mortality, pathology Escherichia coli Infections / enzymology, mortality, pathology Female GTP-Binding Proteins / biosynthesis, deficiency, genetics, physiology* Inflammation Mediators / metabolism, physiology Lipopolysaccharides / toxicity Mice Mice, Inbred C57BL Mice, Knockout Myocardium / enzymology, pathology, ultrastructure Shock, Septic / enzymology*, etiology*, mortality, pathology Survival Analysis Transglutaminases / biosynthesis, deficiency, genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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GGP06254//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Inflammation Mediators; 0/Lipopolysaccharides; EC 2.3.2.-/transglutaminase 2; EC 2.3.2.13/Transglutaminases; EC 3.6.1.-/GTP-Binding Proteins |
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