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标题：Inflammation and skin cholesterol in LDLr-/-, apoA-I-/- mice: link between cholesterol homeostasis and self-tolerance?
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作者：Zabalawi, Manal ; Bharadwaj, Manish ; Horton, Heather 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2007
卷号：48
期号：1
页码：52-65
DOI：10.1194/jlr.M600370-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Diet-fed low density lipoprotein receptor-deficient/apolipoproteinA-I-deficient (LDLr^–/–, apoA-I^–/–) miceaccumulate a 10-fold greater mass of cholesterol in their skindespite a 1.5- to 2-fold lower plasma cholesterol concentrationcompared with diet-fed LDLr^–/– mice. The accumulationof cholesterol predominantly in the skin has been shown to occurin a growing number of other hypercholesterolemic double knockoutmouse models sharing deficits in genes regulating cellular cholesterolhomeostasis. Exploring the relationship between cholesterolbalance and inflammation, we have examined the time course ofcholesterol accumulation in a number of extrahepatic tissuesand correlated with the onset of inflammation in diet-fed LDLr^–/–,apoA-I^–/– mice. After 4 weeks of diet, LDLr^–/–,apoA-I^–/– mice showed a significant increase inskin cholesterol mass compared with LDLr^–/– mice.In addition, after 4 weeks on the diet, cholesterol accumulationin the skin was also found to be associated with macrophageinfiltration and accompanied by increases in tumor necrosisfactor- ${alpha}$ , cyclooxygenase-2, and langerin mRNA, which were notseen in the liver. Overall, these data suggest that as earlyas 4 weeks after starting the diet, the accumulation of skincholesterol and the onset of inflammation occur concurrently.In summary, the use of hypercholesterolemic LDLr^–/–,apoA-I^–/– mice may provide a useful tool to investigatethe role that apoA-I plays in maintaining cholesterol homeostasisand its relationship to inflammation. Supplementary key words apolipoprotein A-I • high density lipoprotein • inflammation • low density lipoprotein receptor-deficient/apolipoprotein A-I-deficient mice • whole body cholesterol • skin • itch