| Budget Amount *help |
¥10,960,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥660,000)
Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2005: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Research Abstract |
Cecal ligation and puncture induced severe sepsis in both wild type and CX3CR1 deficient mice. However, the mortality was higher in CX3CR1 deficient mice with the impairment of intraperitoneal bacterial clearance, compared with WT mice. Moreover, peritoneal macrophages derived from CX3CR1 deficient mice showed reduced bactericidal activity. CX3CR1-mediated signals play a protective role through the enhancement of bactericidal activity in macrophages.
Immunohistochemical detection of CCR2 and CX3CR1 in lungs obtained from autopsy cases. In sepsis cases, CCR2- and CX3CR1-positive macrophages were more frequently detected compared with control cases.
In acetaminophen-induced liver injury, both neutrophils and macrophages were recruited. Neutrophils and macrophages produced iNOS, an injurious factor, and HO-1, a protective factor, respectively. These observations implied opposite roles of neutrophils and macrophages in the pathogenesis of acetaminophen-induced acute liver injury.
TFN-gamma (-
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/-) mice exhibited exacerbated cerulein-induced pancreatic injury, with enhanced neutrophil recruitment. In comparison with WT mice, IFN-gamma (-/-) mice exhibited exaggerated and prolonged NF-kappaB activation, probably due to reduced acetylation of Statl. Thus, IFN-gamma can have anti-inflammatory effects on acute pancreatitis by depressing the proinflammatory consequences of NF-kappaB activation.
Subcutaneous injection of sodium arsenite (NaAs,12.5mg/kg) into BALB/c [wild-type(WT)] mice causes acute renal dysfunction characterized by severe hemorrhages, acute tubular necrosis, and cast formation, with increases in serum blood urea nitrogen and creatinine levels. IFN-gamma-deficient (IFN-gamma-/-) mice exhibited exaggerated renal injury. The intrarenal arsenic concentration was significantly higher in IFN-gamma-/- mice later than10hours after NaAs treatment, with attenuated intrarenal expression of multidrug resistance-associated protein (MRP) 1, a main transporter far NaAs efflux. Thus, IFN-gamma can protect against NaAs-induced acute renal injury, probably by maintaining Nrf2-mediated intrarenal MRP1 gene expression. Less
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