Medicine and Health Sciences Commons^™

Alcohol And Hcv: Implications For Liver Cancer, Gyongyi Szabo, Banishree Saha, Terence Bukong

Gyongyi Szabo

Liver cancers are one of the deadliest known malignancies which are increasingly becoming a major public health problem in both developed and developing countries. Overwhelming evidence suggests a strong role of infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, as well as metabolic diseases such as obesity and diabetes either individually or synergistically to cause or exacerbate the development of liver cancers. Although numerous etiologic mechanisms for liver cancer development have been advanced and well characterized, the lack of definite curative treatments means that gaps in knowledge still exist in identifying key molecular mechanisms and pathways …

Binge Ethanol And Liver: New Molecular Developments, Shivendra Shukla, Stephen Pruett, Gyongyi Szabo, Gavin Arteel

Gyongyi Szabo

Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also …

Ethanol Facilitates Hcv Replication Via Upregulation Of Gw182 And Hsp90 In Human Hepatoma Cells, Terence Bukong, Wei Hou, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Alcohol use and hepatitis C virus (HCV) infection synergize to cause liver damage and microRNA-122 (miR-122) appears to play a key role in this process. Argonaute 2 (Ago2), a key component of the RNA-induced silencing complex, has been shown to be important in modulating miR-122 function during HCV infection. However, GW182, a critical component of processing bodies (GW-bodies) that is recruited by Ago2 to target mRNA has not been assessed in HCV infection. To characterize the role of GW182 in the pathogenesis of HCV infection, we determined its transcription and protein expression in an HCV J6/JFH1 culture system. Here we …

Regulatory Potential Of Ethanol And Retinoic Acid On Human Monocyte Functions, Gyongyi Szabo, Maria Puppolo, Bikash Verma, Donna Catalano

Gyongyi Szabo

Retinoic acid (RA), a metabolic product of vitamin A, has been shown to affect a variety of immune functions, including monocytes. Monocyte functions and mediator production are also modulated by ethanol exposure. This study demonstrates that therapeutic doses of RA (0.1-10 microM) significantly increase transforming growth factor-beta (TGF beta) production both in THP-1, human myelomonocytic cells, and in human peripheral blood monocytes. We have previously reported TGF beta induction by ethanol in human M theta. Combination of RA stimulation with acute in vitro ethanol treatment, however, resulted in significantly lower M theta TGF beta production than TGF beta levels induced …

Alcohol's Contribution To Compromised Immunity, Gyongyi Szabo

Gyongyi Szabo

Alcoholics frequently suffer from infectious diseases and have increased rates of some cancers, indicating that alcohol impairs the immune system, which protects the body against this type of damage. Alcohol interferes with the functions of many of the cells and molecules that are part of the immune system. For example, alcohol inhibits the functions of the cells that ingest and destroy invading microorganisms (i.e., neutrophils, monocytes, and macrophages). Both acute and chronic alcohol exposure also alter the production of signaling molecules that help coordinate the immune response (i.e., cytokines). Finally, alcohol adversely affects the functions of the cells that mediate …

Acute Alcohol Consumption Attenuates Interleukin-8 (Il-8) And Monocyte Chemoattractant Peptide-1 (Mcp-1) Induction In Response To Ex Vivo Stimulation, Gyongyi Szabo, Sangeeta Chavan, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.

A Recent Perspective On Alcohol, Immunity, And Host Defense, Gyongyi Szabo, Pranoti Mandrekar

Gyongyi Szabo

BACKGROUND: Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system.

METHODS: Medline and PubMed databases were used to identify published reports with particular interest in the period of 2000-2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity.

RESULTS: This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The …

Human Monocyte Il-10 Production Is Increased By Acute Ethanol Treatment, Pranoti Mandrekar, Donna Catalano, Linda Girouard, Gyongyi Szabo

Gyongyi Szabo

Immune alterations after acute ethanol treatment are characterized by abnormal monocyte mediator production and antigen presentation capacity. Here, we tested the hypothesis that some of the regulatory effects of ethanol on monocyte functions are mediated by elevated M phi IL-10 production. Physiologically relevant in vitro doses of ethanol (25-100 mM) resulted in significantly increased IL-10 secretion by normal blood monocytes after 18 h stimulation. We found that monocyte IL-10 production induced by either ethanol or LPS increased at 10 h, maximized at 18 h and decreased by 40 h post-stimulation. Furthermore, ethanol significantly augmented LPS-induced monocyte IL-10 secretion at 18 …

Down-Regulation Of Tumor Necrosis Factor Alpha Activity By Acute Ethanol Treatment In Human Peripheral Blood Monocytes, Bikash Verma, Miklos Fogarasi, Gyongyi Szabo

Gyongyi Szabo

As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor alpha (TNF alpha) production in human peripheral blood monocytes (M phi) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF alpha in M phi, it was a potent down-regulator of M phi TNF alpha production whether induced by the combination of interferon-gamma plus muramyl dipeptide (MDP) (P < 0.001), lipopolysaccharide (LPS) alone (P < 0.01), or interferon-gamma plus LPS. Down-regulation of M phi TNF alpha by ethanol was dose dependent and statistically significant in the biologically relevant, 25-150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M phi viability. TNF alpha down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective--though to a lesser extent--if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF alpha production of the in vivo preactivated M phi of trauma patients, which produce hyperelevated levels of TNF alpha. We have previously shown that the majority of posttrauma elevated M phi TNF alpha is produced by the M phi subpopulation expressing high-affinity type I Fc gamma receptors (Fc gamma RI). When the Fc gamma RI cross-linking-stimulated M phi subpopulation was treated with acute ethanol, TNF alpha production was suppressed again both in in vivo preactivated M phi of trauma patients and in M phi of normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Moderate Alcohol Intake In Humans Attenuates Monocyte Inflammatory Responses: Inhibition Of Nuclear Regulatory Factor Kappa B And Induction Of Interleukin 10, Pranoti Mandrekar, Donna Catalano, Bernadette White, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor kappaB (NF-kappaB) binding in human monocytes. METHODS: Human blood monocytes were isolated by plastic adherence before and …