It is widely accepted that stimulation of reverse cholesterol transport, the efflux of excess cholesterol from peripheral tissues and transferring it to the liver for biliary excretion, is becoming an important component in reducing excess cholesterol deposition in atherosclerotic plaques. The ATP-binding cassette transporter has been identified as a key regulator of macrophage cholesterol efflux and apoAI-mediated reverse cholesterol transport. In vivo studies have documented anthocyanins, a large group of naturally phenolic compounds rich in plants, possess substantial capacities in improving plasma cholesterol levels. In this study, we investigated the potential role of anthocyanins in modulating cholesterol efflux from mouse peritoneal macrophages and macrophage-derived foam cells and the possible molecular mechanism linking ABCA1 to cholesterol efflux. Incubation of the mouse peritoneal macrophages and macrophage-derived foam cells with cyanidin-3-O-␤-glucoside and peonidin-3-O-␤-glucoside led to dose-dependent (1-100 M) induction in cholesterol efflux and ABCA1 mRNA expression, and this effect could be blocked by the ABCA1 inhibitor 4,4-diisothiocyanatostilbene-2,2-disulfonic acid, disodium salt, and a general inhibitor of gene transcription actinomycin D. Treatment of the macrophages with anthocyanins also activated peroxisome proliferator-activated receptor ␥, liver X receptor ␣ mRNA expression, and their mediated gene expression. Addition of geranylgeranyl pyrophosphate ammonium salt or GW9662 markedly inhibited the anthocyanin-induced increase of ABCA1 gene expression and apoAI-mediated cholesterol efflux. These data demonstrated that anthocyanin induces cholesterol efflux from mouse peritoneal macrophages and macrophage-derived foam cells and that stimulation of cholesterol efflux by anthocyanin is mediated, at least in part, by peroxisome proliferator-activated receptor ␥-liver X receptor ␣-ABCA1 signaling pathway activation. Atherosclerosis (AS)2 is a multifactorial cardiovascular disease, and its pathogenesis is not fully demonstrated (1, 2). Many studies (3,4) suggested that macrophages played critical pathogenic roles in the formation of atherosclerotic lesions. Fatty streaks of atherosclerosis contain large numbers of macrophage foam cells derived from circulating monocytes that adhere to activated endothelium and migrate into the artery wall (5). These cells subsequently differentiate into macrophages that express the scavenger receptor A gene, as well as other scavenger receptors that mediate the uptake of large amounts of cholesterol (6). As these receptors are not subject to negative regulation by high levels of intracellular cholesterol, massive accumulation of cholesterol esters can occur in macrophages, resulting in foam cell formation. This pathophysiological phenomenon is the typical character of the early stage in the development of AS. Now, it is widely accepted that the removal of excess free cholesterol from arterial cells is very important for maintaining cellular cholesterol homeo...

ABSTRACT. We investigated the association between 3 main proinflammatory cytokines [interleukin (IL)-1b and IL-6] and the risk of acute pancreatitis. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype IL-1β +3954 C/T (rs1143634) and IL-1β -511 C/T (rs16944) and IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796). The genotype distributions of IL-1β +3954 C/T (rs1143634) and IL-1β -511 C/T (rs16944) and IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796) were in HardyWeinberg equilibrium for the control group. Multivariate regression analyses showed that subjects carrying the rs1143634 TT genotype had a significantly increased risk of acute pancreatitis, with an adjusted odds ratio (95% confidence interval) of 2.11 (1.03-4.51). Subjects carrying the IL-1β rs1143634 TT genotype had a significantly increased risk of acute pancreatitis in our Chinese population.