We conclude that polymorphisms in Naip5 are involved in the permissiveness differences of mouse macrophages for intracellular Legionella replication. We speculate that Naip5 is a functional mammalian homolog of plant "resistance" proteins that monitor for, and initiate host response to, the presence of secreted bacterial virulence proteins.
RNA from the region of the genome encoding herpes simplex virus type 1 latency-associated transcripts (LATs) expressed during lytic infection yields low abundances of both polyadenylated and nonpolyadenylated forms. As has been previously shown for latent infection (A
Cholesterol 7␣-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the pathway responsible for the formation of the majority of bile acids. Transcription of the gene is regulated by the size of the bile acid pool and dietary and hormonal factors. The farnesoid X receptor and the liver X receptor (LXR) are responsible for regulation by bile acids and cholesterol, respectively. To study the effects of dietary cholesterol and fat upon expression of the human CYP7A1 gene, mice were generated by crossing transgenic mice carrying the human CYP7A1 gene with mice that were homozygous knockouts (CYP7A1 ؊/؊ ). The mice (mCYP7A1 ؊/؊ /hCYP7A1) expressed the human gene at much higher levels than did the transgenics bred in the wild-type background. A diet containing 1% cholic acid reduced the expression of the human gene in mCYP7A1 ؊/؊ /hCYP7A1 mice to undetectable levels. Cholestyramine (5%) increased the level of expression of the human gene and the mouse gene. Thus, farnesoid X receptor-mediated regulation was preserved. A diet containing 2% cholesterol increased expression of the mouse gene in wild-type mice, but it did not affect expression of the human gene in mCYP7A1 ؊/؊ /hCYP7A1 mice. None of the diets altered the serum cholesterol or triglyceride levels in these mice; 1% cholic acid caused a redistribution of cholesterol from the high density lipoprotein to the low density lipoprotein density in the humanized mice but not in wild-type mice. A diet containing 30% saturated fat and 2% cholesterol caused a decrease in CYP7A1 levels in mCYP7A1 ؊/؊ /hCYP7A1 mice. The serum cholesterol levels rose in all mice fed this diet. The increase was greater in the mCYP7A1 ؊/؊ /hCYP7A1 mice. Together, these data suggest that the lack of an LXR element in the region from ؊56 to ؊49 of the human CYP7A1 promoter may account for some of the differences in response to diets between humans and rodents.Cholesterol is a lipid molecule that plays unique and specific roles in cellular membrane function and embryonic development. It also serves as a precursor for the synthesis of steroid hormones and bile acids. Accordingly, a sophisticated system has evolved to ensure its availability to cells. The liver plays a central role in coordinating many of the components of this process. The accumulation of excess cholesterol in blood vessels leads to atherosclerosis and its accumulation in the bile leads to gallstones. Humans, in contrast to rodents, are highly susceptible to these conditions. Hepatic cholesterol homeostasis is controlled by the rate of cholesterol entry to the liver from dietary and endogenous lipoproteins, as well as by the rate of synthesis of new cholesterol relative to the rate of hepatic lipoprotein secretion, the rate of cholesterol degradation to bile acids, and the rate of excretion of the intact molecule into the bile. These various processes are modulated by the levels of the enzymes catalyzing the rate-limiting steps of each process. An important determinant of the level of these proteins is the rate of transcripti...
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