342 LIVER INJURY AND DEVELOPMENT OF SERUM ANTIMITOCHONDRIAL AUTOANTIBODIES IN AE2A,B-DEFICIENT MICE ARE ASSOCIATED WITH LOW LEVELS OF GLUTATHIONE AND INCREASED APOPTOSIS

2012 ◽  
Vol 56 ◽  
pp. S139
Author(s):  
A. Ferrer ◽  
S. Sarvide ◽  
A. Portu ◽  
J. Salas ◽  
J. Prieto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Low Levels ◽  
Deficient Mice

scholarly journals Alleviation of lipopolysaccharide/ d -galactosamine-induced liver injury in leukocyte cell-derived chemotaxin 2 deficient mice

2017 ◽  
Vol 12 ◽  
pp. 166-171 ◽  
Author(s):  
Akinori Okumura ◽  
Takeshi Saito ◽  
Minoru Tobiume ◽  
Yuki Hashimoto ◽  
Yuko Sato ◽  
...  
Keyword(s):  
Liver Injury ◽  
Deficient Mice

Cholestatic IL-12 deficient mice are resistant to endotoxin induced liver injury and shock

2001 ◽  
Vol 120 (5) ◽  
pp. A28
Author(s):  
Miguel E. Sewnath ◽  
Tom Poll ◽  
Fiebo J.W. Kate ◽  
Dirk J. Gouma
Keyword(s):  
Liver Injury ◽  
Deficient Mice

A γGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice

2004 ◽  
Vol 18 (3) ◽  
pp. 290-298 ◽  
Author(s):  
Thu H. Le ◽  
Michael I. Oliverio ◽  
Hyung-Suk Kim ◽  
Harmony Salzler ◽  
Rajesh C. Dash ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Transgenic Mice ◽  
Proximal Tubule ◽  
Physiological Role ◽  
Renal Proximal Tubule ◽  
Hypoxanthine Phosphoribosyl Transferase ◽  
Wild Type ◽  
Specific Expression ◽  
Low Levels ◽  
Deficient Mice

To understand the physiological role of angiotensin type 1 (AT1) receptors in the proximal tubule of the kidney, we generated a transgenic mouse line in which the major murine AT1 receptor isoform, AT1A, was expressed under the control of the P1 portion of the γ-glutamyl transpeptidase (γGT) promoter. In transgenic mice, this promoter has been shown to confer cell-specific expression in epithelial cells of the renal proximal tubule. To avoid random integration of multiple copies of the transgene, we used gene targeting to produce mice with a single-copy transgene insertion at the hypoxanthine phosphoribosyl transferase ( Hprt) locus on the X chromosome. The physiological effects of the γGT-AT1A transgene were examined on a wild-type background and in mice with targeted disruption of one or both of the murine AT1 receptor genes ( Agtr1a and Agtr1b). On all three backgrounds, γGT-AT1A transgenic mice were healthy and viable. On the wild-type background, the presence of the transgene did not affect development, blood pressure, or kidney structure. Despite relatively low levels of expression in the proximal tubule, the transgene blunted the increase in renin expression typically seen in AT1-deficient mice and partially rescued the kidney phenotype associated with Agtr1a−/− Agtr1b−/− mice, significantly reducing cortical cyst formation by more than threefold. However, these low levels of cell-specific expression of AT1 receptors in the renal proximal tubule did not increase the low blood pressures or abolish sodium sensitivity, which are characteristic of AT1 receptor-deficient mice. Although our studies do not clearly identify a role for AT1 receptors in the proximal tubules of the kidney in blood pressure homeostasis, they support a major role for these receptors in modulating renin expression and in maintaining structural integrity of the renal cortex.

Time-dependent platelet-vessel wall interactions induced by intestinal ischemia-reperfusion

2003 ◽  
Vol 284 (6) ◽  
pp. G1027-G1033 ◽  
Author(s):  
Dianne Cooper ◽  
Keith D. Chitman ◽  
Matthew C. Williams ◽  
D. Neil Granger
Keyword(s):  
Time Course ◽  
Platelet Adhesion ◽  
Ischemia Reperfusion ◽  
Time Dependent ◽  
Wild Type ◽  
Blocking Antibody ◽  
Low Levels ◽  
Intestinal Ischemia Reperfusion ◽  
Deficient Mice ◽  
Platelet Depletion

Platelets roll and adhere in venules exposed to ischemia-reperfusion (I/R). This platelet-endothelial adhesion may influence leukocyte trafficking because platelet depletion decreases I/R-induced leukocyte emigration. The objectives of this study were 1) to assess the time course of platelet adhesion in the small bowel after I/R and 2) to determine the roles of endothelial and/or platelet P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) in this adhesion. The adhesion of fluorescently labeled platelets was monitored by intravital microscopy in postcapillary venules exposed to 45 min of ischemia and up to 8 h of reperfusion. Peak platelet adhesion was observed at 4 h of reperfusion. To assess the contributions of platelet and endothelial cell P-selectin, platelets from P-selectin-deficient and wild-type mice were infused into wild-type and P-selectin-deficient mice, respectively. Platelets deficient in P-selectin exhibited low levels of adhesion comparable to that in sham-treated animals. In the absence of endothelial P-selectin, platelet adhesion was reduced by 65%. Treatment with a blocking antibody against PSGL-1 reduced adhesion by 57%. These results indicate that I/R induces a time-dependent platelet-endothelial adhesion response in postcapillary venules via a mechanism that involves PSGL-1 and both platelet and endothelial P-selectin, with platelet P-selectin playing a greater role.

Tubastatin-A Mediated Protection from Acetaminophen-Induced Liver Injury is Preserved in Lymphocyte and Macrophage Deficient Mice

2020 ◽  
Vol 231 (4) ◽  
pp. e224
Author(s):  
Ciaran O'Brien ◽  
Paul Hernandez ◽  
Seth Concors ◽  
Guanghui Ge ◽  
Zhonglin Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Deficient Mice

scholarly journals IL-18-deficient mice are resistant to endotoxin-induced liver injury but highly susceptible to endotoxin shock

1999 ◽  
Vol 11 (3) ◽  
pp. 471-480 ◽  
Author(s):  
Yoshimitsu Sakao ◽  
Kiyoshi Takeda ◽  
Hiroko Tsutsui ◽  
Tsuneyasu Kaisho ◽  
Fumiko Nomura ◽  
...  
Keyword(s):  
Liver Injury ◽  
Endotoxin Shock ◽  
Deficient Mice

scholarly journals TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration

2015 ◽  
Vol 309 (1) ◽  
pp. G30-G41 ◽  
Author(s):  
Yoon Seok Roh ◽  
Bi Zhang ◽  
Rohit Loomba ◽  
Ekihiro Seki
Keyword(s):  
Liver Injury ◽  
Alcoholic Hepatitis ◽  
Early Stage ◽  
Neutrophil Infiltration ◽  
Wild Type ◽  
Ethanol Feeding ◽  
Binge Ethanol ◽  
Deficient Mice ◽  
Cxcl1 Expression

Although previous studies reported the involvement of the TLR4-TRIF pathway in alcohol-induced liver injury, the role of TLR2 and TLR9 signaling in alcohol-mediated neutrophil infiltration and liver injury has not been elucidated. Since alcohol binge drinking is recognized to induce more severe form of alcohol liver disease, we used a chronic-binge ethanol-feeding model as a mouse model for early stage of alcoholic hepatitis. Whereas a chronic-binge ethanol feeding induced alcohol-mediated liver injury in wild-type mice, TLR2- and TLR9-deficient mice showed reduced liver injury. Induction of neutrophil-recruiting chemokines, including Cxcl1, Cxcl2, and Cxcl5, and hepatic neutrophil infiltration were increased in wild-type mice, but not in TLR2- and TLR9-deficient mice. In vivo depletion of Kupffer cells (KCs) by liposomal clodronate reduced liver injury and the expression of Il1b, but not Cxcl1, Cxcl2, and Cxcl5, suggesting that KCs are partly associated with liver injury, but not neutrophil recruitment, in a chronic-binge ethanol-feeding model. Notably, hepatocytes and hepatic stellate cells (HSCs) produce high amounts of CXCL1 in ethanol-treated mice. The treatment with TLR2 and TLR9 ligands synergistically upregulated CXCL1 expression in hepatocytes. Moreover, the inhibitors for CXCR2, a receptor for CXCL1, and MyD88 suppressed neutrophil infiltration and liver injury induced by chronic-binge ethanol treatment. Consistent with the above findings, hepatic CXCL1 expression was highly upregulated in patients with alcoholic hepatitis. In a chronic-binge ethanol-feeding model, the TLR2 and TLR9-dependent MyD88-dependent pathway mediates CXCL1 production in hepatocytes and HSCs; the CXCL1 then promotes neutrophil infiltration into the liver via CXCR2, resulting in the development of alcohol-mediated liver injury.

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