Impairment of vascular function following BCG immunisation is associated with immune responses to HSP-60 in the cholesterol-fed rabbit.

An immune response to heat shock protein (HSP)-60/65 has recently been implicated in atherogenesis. The aim of this study was to determine whether this effect may be mediated by impairment of endothelial function. Rabbits were injected with bacillus Calmette-Guerin (BCG) vaccine (n=12) or saline (n=12).

Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation.

Atherosclerosis has long been recognised as having an inflammatory component, and this has a particularly important bearing on to its clinical complications as it may result in plaque instability. Results of recent epidemiological studies have reinforced the potential importance of this aspect of the disease. Positive associations have been reported between exposure to several specific pathogens, and future risk of coronary heart disease (CHD).

Receptor-dependent regulation of the CYP3A4 gene.

A CYP3A4 promoter-reporter gene construct has been used to assess the ability of 16 known (in vivo) and putative (in vitro) inducers to transactivate a CYP3A4 reporter gene in HepG2 cells. With the exception of pravastatin, the remaining 15 compounds transactivated the CYP3A4 reporter gene with differing inductive abilities (I(max):EC(50)) over two orders of magnitude, ranging from 1.1 (phenytoin) to 222.

Glucocorticoid-mediated induction of CYP3A4 is decreased by disruption of a protein: DNA interaction distinct from the pregnane X receptor response element.

CYP3A4 is the most abundant cytochrome P450 (P450) in human liver, comprising approximately 30% of the total liver P450 content. This enzyme has an important role in steroid catabolism and metabolism of foreign compounds, with the majority of pharmaceutical compounds being substrates for CYP3A4. The molecular mechanisms that underlie transcriptional activation of CYP3A4 are complex with many steroid hormone nuclear receptors, including glucocorticoid receptor, pregnane X receptor (PXR), vitamin D receptor, and constitutive androstane receptor, playing roles.