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-kappa B 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.

Falasca, L., Farrace, M.g., Rinaldi, A., Tuosto, L., Melino, G., Piacentini, M. (2008). Transglutaminase type II is involved in the pathogenesis of endotoxic shock. JOURNAL OF IMMUNOLOGY, 180(4), 2616-2624.

Transglutaminase type II is involved in the pathogenesis of endotoxic shock

FARRACE, MARIA GRAZIA;MELINO, GENNARO;PIACENTINI, MAURO
2008-01-01

Abstract

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-kappa B 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.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
immunoglobulin enhancer binding protein; lipopolysaccharide; protein glutamine gamma glutamyltransferase 2; autacoid; guanine nucleotide binding protein; protein glutamine gamma glutamyltransferase; transglutaminase 2; animal cell; animal experiment; animal model; animal tissue; article; controlled study; endotoxemia; enzyme inhibition; female; homeostasis; in vivo study; infection resistance; kidney; knockout mouse; mouse; neutrophil chemotaxis; nonhuman; organ injury; pathogenesis; peritoneum; priority journal; protein expression; protein function; septic shock; survival rate; wild type; acute kidney failure; animal; biosynthesis; C57BL mouse; Enterobacter infection; enzymology; genetics; heart muscle; metabolism; mortality; mouse mutant; pathology; physiology; survival; ultrastructure; Animals; Endotoxemia; Escherichia coli Infections; Female; GTP-Binding Proteins; Inflammation Mediators; Kidney Failure, Acute; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Shock, Septic; Survival Analysis; Transglutaminases
PMID: 18250473
Falasca, L., Farrace, M.g., Rinaldi, A., Tuosto, L., Melino, G., Piacentini, M. (2008). Transglutaminase type II is involved in the pathogenesis of endotoxic shock. JOURNAL OF IMMUNOLOGY, 180(4), 2616-2624.
Falasca, L; Farrace, Mg; Rinaldi, A; Tuosto, L; Melino, G; Piacentini, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/30420
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