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In response to infection, inflammation, or injury, the neural-immune-endocrine networks are activated to restore or maintain stability in the internal environment. Disruption of any one of the functional components may impair the effectiveness of the immune response to challenges, and may consequently jeopardize the wellness of the host. Studies in the author's laboratory have shown that the normal...
This study was designed to test the hypothesis that the activity and expression of iNOS in the ileum will be altered in young rats exposed to alcohol in utero (FAE). The subjects, 26-29-day-old rats, were progeny of dams fed an alcohol diet during gestation and their pair-fed/control cohorts. We determined the effects of endotoxin administration on ileal iNOS enzymatic activity and on ileal iNOS immunoreactivity...
Both chronic and acute ethanol exposure have been shown to be cytotoxic and also to disrupt normal cell function or responses in a variety of cell types. Macrophage function has specifically been shown to be disrupted by chronic ethanol exposure by mechanisms that have not been elucidated. It is known that exposure of macrophages to lipopolysaccharide (LPS) from gram-negative bacteria will decrease...
The mechanisms underlying alcoholic liver disease are not fully understood. It has been established that alcohol interferes with transcriptional and translational regulatory steps of cell function. To understand such an effect, assessment of alcohol-induced changes in the simultaneous expression of a large number of genes may prove very useful. The purpose of the current study was to test a large...
Tumor necrosis factor-alpha (TNF-α) is one of a number of cytokines implicated in the progression of alcohol-induced liver disease. Activation of hepatic macrophages by lipopolysaccharide (LPS) during exposure to ethanol is thought to be an important mechanism for stimulation of TNF-α expression. Chronic exposure of macrophages to ethanol, both in vivo after ad libitum feeding of ethanol for 4 weeks...
Ethanol suppresses innate resistance to a variety of microbes, and findings of studies from both our laboratory and other laboratories indicate suppression of responses is mediated through two Toll-like receptors (TLRs): TLR3 and TLR4. In this article, we review recent findings from studies in our laboratory, indicating that ethanol also suppresses responses mediated through other TLRs. Considering...
Several recent studies have documented that signaling can be fundamentally different in vivo and in vitro. However, studies of signaling and cytokine production by macrophages are often conducted in vitro, without confirmation in vivo. In addition, the direct effects of drugs and chemicals, including ethanol, on these processes are also often investigated in vitro. The purpose of the present study...
Alcohol abuse impairs the pulmonary immune response to infection and increases the morbidity and mortality of bacterial pneumonia. Acute alcohol intoxication suppresses lung expression of CXC chemokines bearing the Glu-Leu-Arg motif (ELR + ) following lipopolysaccharide (LPS) challenge, but its effect on the structurally related ELR − CXC chemokines, which attract T cells, is unknown...
Chronic alcoholics are predisposed to the development of a systemic inflammatory response syndrome, which is usually triggered in the gut. This study aimed to investigate in rats the role of intestinal epithelial inflammatory responsiveness in the susceptibility of alcoholics to excessive inflammation. Thirty Wistar rats were randomly divided into three groups: 10 rats killed immediately after acclimation...
Excess alcohol intake, as in binge drinking, increases susceptibility to microbial pathogens. Alcohol impairs macrophage function by suppression of the Toll-like receptor 4 (TLR4) pathway. This study investigated the effects of acute ethanol intake on the TLR4 pathway in rat intestinal epithelia, which usually encounters luminal antigens at first and participates in the development of intestinal immunity...
Microglia undergo maturation during the third trimester of human development (equivalent to the first 1–2 weeks of postnatal life in rodents), during which these cells may be particularly sensitive to insult. Alcohol exposure during this period can activate the neuroimmune system, an effect that may contribute to the pathophysiology of fetal alcohol spectrum disorders. Here, we investigated whether...
Neuroinflammation may play an important role in the development of alcohol addiction. Recent preclinical reports suggest that enhanced innate immune system signaling increases consumption of alcohol. Our aim was to study whether consequences of lipopolysaccharide (LPS)-induced sickness reaction increase long-term alcohol intake. Adult male C57BL/6J mice, housed in individually ventilated cages, were...
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