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Full-Text Articles in Rheumatology

Increased Lipopolysaccharide Sensitivity In Alcoholic Fatty Livers Is Independent Of Leptin Deficiency And Toll-Like Receptor 4 (Tlr4) Or Tlr2 Mrna Expression, Laszlo Romics, Pranoti Mandrekar, Karen Kodys, Arumugam Velayudham, Yvonne Drechsler, Angela Dolganiuc, Gyongyi Szabo Apr 2010

Increased Lipopolysaccharide Sensitivity In Alcoholic Fatty Livers Is Independent Of Leptin Deficiency And Toll-Like Receptor 4 (Tlr4) Or Tlr2 Mrna Expression, Laszlo Romics, Pranoti Mandrekar, Karen Kodys, Arumugam Velayudham, Yvonne Drechsler, Angela Dolganiuc, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Both alcoholic (AFL) and nonalcoholic (NAFL) fatty livers show increased sensitivity to endotoxin-induced injury. Lipopolysaccharide (LPS) is recognized by toll-like receptor 4 (TLR4), whereas lipopeptide triggers TLR2 to induce common downstream activation of nuclear factor (NF)-kappaB and pro-inflammatory pathways that are activated in AFL and NAFL. METHODS: Serum alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels; hepatic NF-kappaB activity; and expression of TLR2, TLR4, inducible nitric oxide synthase (iNOS), and heme oxygenase (HO)-1 mRNAs were investigated in lean and leptin-deficient ob/ob mice after LPS challenge in combination with acute or chronic alcohol feeding. RESULTS: Increased LPS …


Acute Alcohol Activates Stat3, Ap-1, And Sp-1 Transcription Factors Via The Family Of Src Kinases To Promote Il-10 Production In Human Monocytes, Oxana Norkina, Angela Dolganiuc, Taryn Shapiro, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo Apr 2010

Acute Alcohol Activates Stat3, Ap-1, And Sp-1 Transcription Factors Via The Family Of Src Kinases To Promote Il-10 Production In Human Monocytes, Oxana Norkina, Angela Dolganiuc, Taryn Shapiro, Karen Kodys, Pranoti Mandrekar, Gyongyi Szabo

Gyongyi Szabo

Alcohol consumption is associated with an imbalance in pro- and anti-inflammatory cytokines and immunosuppression, partially as a result of enhanced IL-10 production. The mechanisms of IL-10 induction by alcohol remain poorly understood. We identified that increased IL-10 production in human monocytes after acute in vivo alcohol consumption or in vitro alcohol treatment was associated with increased STAT3 activation. Alcohol alone induced and in combination with LPS augmented STAT3 phosphorylation at tyrosine 705 (tyr705) and serine 727 (ser727) residues and increased STAT3 binding to DNA. Upstream, alcohol activated the Src kinases, as indicated by an increase in phosphorylated and a decrease …


Inhibition Of Lipopolysaccharide-Mediated Nfkappab Activation By Ethanol In Human Monocytes, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo Apr 2010

Inhibition Of Lipopolysaccharide-Mediated Nfkappab Activation By Ethanol In Human Monocytes, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Alcohol use is typically associated with impaired immunity and increased host susceptibility to infection, partially due to decreased inflammatory response. Acute ethanol exposure has been shown to down-regulate monocyte production of inflammatory cytokines. Activation of the pluripotent transcription factor NFkappaB is a pivotal step in the induction of inflammatory cytokines, chemokines and growth factors. Therefore, we hypothesized that alcohol may alter NFkappaB activation, thus providing a mechanism for the decreased inflammatory cytokine production by monocytes after acute alcohol treatment. We show here for the first time that alcohol inhibits lipopolysaccharide (LPS)-induced NFkappaB activation in human monocytes by decreasing DNA binding …