Divergent results induced by different types of septic shock in transglutaminase 2 knockout mice.
Acute sepsis can be induced by cytokines such as TNF-α and biological products such as LPS. All of these agents cause systemic inflammation, which is characterized by hemodynamic shock and liver toxicity. However, the outcomes of different septic shock models were totally opposite in transglutaminase 2 knockout (TGase 2(-/-)) mice. The aim of our study was to clarify the role of TGase 2 in liver injury. Therefore, we explored the role of TGase 2 in liver damage using two different stress models: LPS-induced endotoxic shock and TNF-α/actinomycin D (ActD)-induced sepsis. TNF-α-dependent septic shock resulted in increased liver damage in TGase 2(-/-) mice compared with wild-type (WT) mice, and was accompanied by increased levels of caspase 3 and cathepsin D (CTSD) in the damaged liver. Conversely, LPS-induced septic shock resulted in ablation of inflammatory endotoxic shock in TGase 2(-/-) mice and decreased liver injury. We found that TGase 2 protected liver tissue from TNF-α-dependent septic shock by reducing the expression of caspase 3 and CTSD. However, TGase 2 differently participated in increased the hemodynamic shock in LPS-induced septic shock through macrophage activation rather than protecting direct liver damage. Therefore, these findings demonstrate that septic shock caused by different agents may induce different results in TGase 2(-/-) mice depending on the primary target organs affected.
Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Republic of Korea.
Hyun
H
Yoo
Eu-Ree
ER
Ahn
Se-Jin
SJ
Kim
Seon-Hyeong
SH
Lee
Seung Hyun
SH
Oh
Soo-Youl
SY
Kim
D000818:Animals; D017209:Apoptosis; D002402:Cathepsin D / Q000378:metabolism; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D005688:Galactosamine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012772:Shock, Septic / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D011503:Transglutaminases / Q000172:deficiency / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D005688:Galactosamine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D002402:Cathepsin D; C533923:Ctsd protein, mouse; D019204:GTP-Binding Proteins