Homework SourseWhat is the hypothesis in this paragraph Infectionassociated
What is the hypothesis in this paragraph?
\"Infection-associated in?ammation can alter the expression levels and functions of cytochrome P450s
(CYPs). Cyp gene expression is regulated by the activation of several nuclear receptors, including pregnane X
receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR). These recep-
tors can be activated by xenobiotics, including medicines. Here, to study the xenobiotic-induced ?uctuations
in CYP during in?ammation, we examined the effect of lipopolysaccharide (LPS) treatment on the level of
mRNAs encoding hepatic CYPs induced by xenobiotic-activated nuclear receptors, in mice. Both the mRNA
induction of Cyp genes and the metabolic activities of CYP proteins were examined. LPS treatment caused
a signi?cant decrease in the induced expression of the mRNAs for Cyp3a11, 2c29, 2c55, and 1a2, but not for
Cyp2b10. To assess the CYP enzymatic activities, CYP3A-mediated testosterone 6?-hydroxylation and the
intrinsic clearance (CLint) of nifedipine in liver microsomes were measured in mice treated with the xenobi-
otic pregnenolone-16alpha-carbonitrile (PCN) with or without LPS administration. Both assays revealed that
the CYP3A activity, which was induced by PCN, declined signi?cantly after LPS treatment, and this decline
correlated with the Cyp3a11 mRNA level. In addition, we found that the mRNAs for interleukin (IL)-1? and
tumor necrosis factor (TNF) ? were increased after treatment with LPS plus xenobiotics. Our ?ndings dem-
onstrated that LPS treatment reduces the PXR- and AhR-mediated, and possibly CAR-mediated Cyp gene
expression and further suggest that these decreases are dependent on in?ammatory cytokines in the liver.
\"
\"Infection-associated in?ammation can alter the expression levels and functions of cytochrome P450s
(CYPs). Cyp gene expression is regulated by the activation of several nuclear receptors, including pregnane X
receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR). These recep-
tors can be activated by xenobiotics, including medicines. Here, to study the xenobiotic-induced ?uctuations
in CYP during in?ammation, we examined the effect of lipopolysaccharide (LPS) treatment on the level of
mRNAs encoding hepatic CYPs induced by xenobiotic-activated nuclear receptors, in mice. Both the mRNA
induction of Cyp genes and the metabolic activities of CYP proteins were examined. LPS treatment caused
a signi?cant decrease in the induced expression of the mRNAs for Cyp3a11, 2c29, 2c55, and 1a2, but not for
Cyp2b10. To assess the CYP enzymatic activities, CYP3A-mediated testosterone 6?-hydroxylation and the
intrinsic clearance (CLint) of nifedipine in liver microsomes were measured in mice treated with the xenobi-
otic pregnenolone-16alpha-carbonitrile (PCN) with or without LPS administration. Both assays revealed that
the CYP3A activity, which was induced by PCN, declined signi?cantly after LPS treatment, and this decline
correlated with the Cyp3a11 mRNA level. In addition, we found that the mRNAs for interleukin (IL)-1? and
tumor necrosis factor (TNF) ? were increased after treatment with LPS plus xenobiotics. Our ?ndings dem-
onstrated that LPS treatment reduces the PXR- and AhR-mediated, and possibly CAR-mediated Cyp gene
expression and further suggest that these decreases are dependent on in?ammatory cytokines in the liver.
\"
