Commentary with regard to the role of alcohol and cofactors in the development of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary cancer of the liver. It is clear that chronic alcohol abuse is associated with the development of HCC, but the mechanistic role of alcohol in HCC is not well studied. The research that is presented in the Brandon-Warner and colleagues' (2012) article approaches an important outcome of chronic alcohol abuse.

Staphylococcus epidermidis saeR is an effector of anaerobic growth and a mediator of acute inflammation.

The saeRS two-component regulatory system regulates transcription of multiple virulence factors in Staphylococcus aureus. In the present study, we demonstrated that the saePQRS region in Staphylococcus epidermidis is transcriptionally regulated in a temporal manner and is arranged in a manner similar to that previously described for S. aureus.

Association of chronic alcohol consumption and increased susceptibility to and pathogenic effects of pulmonary infection with respiratory syncytial virus in mice.

Chronic alcohol abuse by human beings has been shown to be associated with increased susceptibility to pulmonary infections and severity of inflammatory responses associated with pulmonary infection. On the basis of the higher likelihood of exposure to respiratory viruses, people who abuse alcohol would logically be susceptible to respiratory viral infections. To test this hypothesis, mice were provided alcohol in drinking water for 13-16 weeks with the Meadows-Cook protocol and infected intranasally with respiratory syncytial virus.

Thymocytes, pre-B cells, and organ changes in a mouse model of chronic ethanol ingestion--absence of subset-specific glucocorticoid-induced immune cell loss.

Background: The well-known immune deficiency of the chronic alcoholic dictates the need for a long-term rodent ethanol administration model to evaluate the baseline immunologic effects of chronic ethanol abuse, and investigate the genetic determinants of those effects. Much published work with rodents has shown clearly that acute ethanol administration and short-term ethanol-containing liquid diets both cause elevated corticosterone and can cause significant thymocyte, pre-B cell and peripheral lymphocyte losses. Such losses may mask more subtle alterations in immune homeostasis, and in any case are generally short-lived compared with the span of chronic ethanol abuse.

Alcoholic pancreatitis: mechanisms of viral infections as cofactors in the development of acute and chronic pancreatitis and fibrosis.

Acute and chronic pancreatitis is associated with alcohol abuse, but symptomatic pancreatitis develops in only a small proportion of persons (10-20%) who abuse alcohol. This apparent paradox has led to the notion that additional cofactors are involved in the development of alcoholic pancreatitis. Potential cofactors, such as diet and smoking, have been suggested, but there are no compelling epidemiologic data to support this idea.

Inhibition of protein kinase C epsilon causes ciliated bovine bronchial cell detachment.

This study defines the in vitro phenomenon of ciliated bovine bronchial epithelial cell (BBEC) detachment from the basal epithelium and regulation of cilia motility mediated through protein kinase C epsilon (PKCepsilon). The authors determined the time course of activation and downregulation of PKCepsilon by the known PKC activator phorbol 12-myristate 13-acetate (PMA) and demonstrate that chemical inhibition of PKC by calphostin C or the novel PKC isoform inhibitor Ro 31-8220 induced striking detachment of ciliated BBECs from the basal cell monolayer within 1 hour, independent of apoptosis or necrotic cell death. The results of this study support a possible novel PKCepsilon-mediated signaling pathway through which ciliated cell attachment is maintained.

Acute and chronic alcohol abuse modulate immunity.

This article represents the proceedings of the Alcohol and Immunology Research Interest Group (AIRIG) meeting, a satellite workshop held at the 37th Annual Meeting of the Society for Leukocyte Biology. The meeting was sponsored by the AIRIG and the National Institute on Alcohol Abuse and Alcoholism. The presentations were as follows: (1) Effects of Ethanol on Immune Response to Hepatitis C Virus by Jack R.

Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: role of nonoxidative metabolism.

Chronic alcohol abuse, a major health problem, causes liver and pancreatic diseases and is known to impair hepatic alcohol dehydrogenase (ADH). Hepatic ADH-catalyzed oxidation of ethanol is a major pathway for the ethanol disposition in the body. Hepatic microsomal cytochrome P450 (CYP2E1), induced in chronic alcohol abuse, is also reported to oxidize ethanol.

Rescue of in vivo FAS-induced apoptosis of hepatocytes by corticosteroids either associated with alcohol consumption by mice or provided exogenously.

The pathogenic effects of many hepatic viral infections are mediated, at least in part, by the immune response to the infected hepatocyte. The immune response in the infected liver involves the interaction of cytotoxic T cells (CTL) with the hepatocytes through the interaction of FAS-ligand on the CTL and FAS on the hepatocyte. The initial hypothesis for this study was that alcohol consumption by mice would sensitize the liver to apoptosis induced by ligation of FAS.

Ethanol consumption potentiates viral pancreatitis and may inhibit pancreas regeneration: preliminary findings.

Alcohol abuse is often associated with acute pancreatitis. The pathogenesis of alcoholic pancreatitis remains poorly understood, in part because of the lack of a suitable animal model to study the mechanism or mechanisms of this disease. It has been proposed that ethanol predisposes or sensitizes the pancreas to the effects of co-factors, and the combination of the effects of ethanol on the pancreas and the actions of these co-factors results in alcoholic pancreatitis.

Alcohol and immunology: introduction to and summary of the 2003 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

The 8th Meeting of the Alcohol and Immunology Research Interest Group (AIRIG) was held at Loyola University Medical Center, Maywood, Illinois, USA, on November 21, 2003. Reports from multiple laboratories reveal that the functional integrity of the immune system is of paramount importance to the survival of the individual after infection or injury. Evidence supports the idea that exposure to alcohol causes dysregulation of both the innate and the adaptive arms of the immune system.

Animal model of alcoholic pancreatitis: role of viral infections.

Pancreatitis is clearly associated with alcohol abuse, but only a relatively small percentage of people who abuse alcohol develops obvious pancreatitis. These observations have led to the concept that the development of alcoholic pancreatitis requires cofactors. Although diet and smoking have been studied, a clear cofactor has not been identified.

Modulation of immunity and viral-host interactions by alcohol.

This manuscript represents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers/chairs were Gyongyi Szabo and Geoffrey M. Thiele.

Influence of ethanol consumption on experimental viral hepatitis.

Background: One important contributor to pathologic effects on the liver associated with alcohol abuse is viral hepatitis, especially hepatitis C virus (HCV) infection. Alcohol consumption has been shown to be associated with more severe HCV infection and hepatitis. The mechanisms of the more severe viral infection of the liver are unclear, and studies have been hampered by the lack of an animal model of hepatotropic viral infections.

Role of activated CD8+ T cells in the initiation and continuation of hepatic damage.

The cause of alcoholic liver disease (ALD) is multifactorial and poorly understood. It is clear that alcohol alone is not responsible for most of the changes associated with ALD and that cofactors are involved in initiation and production of ALD. One cofactor that has received a great deal of attention recently is the concomitant infection with hepatitis C virus (HCV) and alcohol abuse.

Association of alcohol consumption and exaggerated immunopathologic effects in the liver induced by infectious organism.

The cause of alcoholic liver disease (ALD) is multifactorial and poorly understood. It is clear that alcohol alone is not responsible for most of the changes associated with ALD and that cofactors are involved in initiation and production of ALD. One cofactor that has received a great deal of attention recently is the concomitant infection with hepatitis C virus (HCV) and alcohol abuse.

Relationship between acetaldehyde levels and cell survival in ethanol-metabolizing hepatoma cells.

We have created a number of recombinant Hep G2 cell lines, designated VA cells, that constitutively express alcohol dehydrogenase. Oxidation of ethanol by the VA cells results in the production and accumulation of acetaldehyde, and a dramatic increase in the nicotinamide adenine dinucleotide, reduced (NADH)/nicotinamide adenine dinucleotide (NAD(+)) ratio (redox-state). It is believed that production of acetaldehyde, and the increase in the redox-state of hepatocytes, are responsible for many of the dysfunctions associated with alcoholic liver disease.

Alcohol consumption is associated with alterations in macrophage responses to interferon-gamma and infection by Salmonella typhimurium.

Abuse of ethanol (EtOH) by human beings and administration of EtOH to experimental animals has been shown to be associated with a suppression of the immune system. Consumption of EtOH has also been associated with an increased incidence and severity of infections of human beings and experimental animals, which has been attributed to the immunosuppression associated with EtOH consumption. It has been shown that EtOH also affects the function of macrophages (MØ), which are important effector cells in the innate and adaptive immune responses to infectious agents.

Initiation of alcoholic fatty liver and hepatic inflammation with a specific recall immune response in alcohol-consuming C57Bl/6 mice.

Whether immunological responses are involved in initiation and progression of alcoholic liver disease is unclear. We describe a mouse model of alcoholic liver injury characterized by steatosis and hepatic inflammation initiated by a recall immune response. Mice immune to Listeria monocytogenes fed a liquid diet containing ethanol and challenged with viable bacteria developed steatosis within 24 h and, at a later time, elevated serum alanine aminotransferase levels, indicating more liver damage in this group.

Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid cells from the gut-associated lymphoid tissues and altered resistance to oral infections with Salmonella typhimurium.

Studies were done to test whether ethanol (ETOH) consumption alters resistance to mucosal and systemic infections by Salmonella typhimurium. S. typhimurium-immune and -nonimmune mice were fed 1 of 3 diets (an ETOH-containing liquid diet, an isocaloric liquid diet equal in volume to that of the ETOH-treated group, or laboratory chow) in a pair-feeding design and were infected orally or intravenously with S.

Effect of adrenalectomy on ethanol-associated changes in lymphocyte cell numbers and subpopulations in thymus, spleen, and gut-associated lymphoid tissues.

Consumption of ethanol (ETOH) by experimental animals and human beings is associated with elevated serum levels of corticosteroids. One of the most robust findings associated with ETOH consumption is a loss of lymphocytes from thymus and spleen, as well as from peripheral lymphoid organs to include mesenteric lymph nodes and Peyer's patches, which are lymphoid organs associated with the gastrointestinal tract. To study the role of corticosteroids in loss of cells from thymus, spleen, and gut-associated lymphoid organs, adrenalectomized (ADX) or intact C57Bl/6 mice were fed a liquid diet containing ETOH (to supply 36% of calories as ETOH) or an isocaloric control diet with a pair-feeding protocol.