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Immunology and Infectious Disease

Macrophages

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The Opposite Effects Of Acute And Chronic Alcohol On Lipopolysaccharide-Induced Inflammation Are Linked To Irak-M In Human Monocytes, Pranoti Mandrekar, Shashi Bala, Donna Catalano, Karen Kodys, Gyongyi Szabo Apr 2010

The Opposite Effects Of Acute And Chronic Alcohol On Lipopolysaccharide-Induced Inflammation Are Linked To Irak-M In Human Monocytes, Pranoti Mandrekar, Shashi Bala, Donna Catalano, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Impaired host defense after alcohol use is linked to altered cytokine production, however, acute and chronic alcohol differently modulate monocyte/macrophage activation. We hypothesized that in human monocytes, acute alcohol induces hyporesponsiveness to LPS, resulting in decreased TNF-alpha, whereas chronic alcohol increases TNF-alpha by sensitization to LPS. We found that acute alcohol increased IL-1R-associated kinase-monocyte (IRAK-M), a negative regulator of IRAK-1, in human monocytes. This was associated with decreased IkappaB alpha kinase activity, NFkappaB DNA binding, and NFkappaB-driven reporter activity after LPS stimulation. In contrast, chronic alcohol decreased IRAK-M expression but increased IRAK-1 and IKK kinase activities, NFkappaB DNA binding, and …


Acute Ethanol Treatment Augments Interleukin-12 Production In Activated Human Monocytes, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano Apr 2010

Acute Ethanol Treatment Augments Interleukin-12 Production In Activated Human Monocytes, Gyongyi Szabo, Linda Girouard, Pranoti Mandrekar, Donna Catalano

Gyongyi Szabo

No abstract provided.


Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano Apr 2010

Regulation Of Human Monocyte Functions By Acute Ethanol Treatment: Decreased Tumor Necrosis Factor-Alpha, Interleukin-1 Beta And Elevated Interleukin-10, And Transforming Growth Factor-Beta Production, Gyongyi Szabo, Pranoti Mandrekar, Linda Girouard, Donna Catalano

Gyongyi Szabo

We and others have previously shown that even acute ethanol exposure has the capacity to modulate immune functions, particularly monocyte functions. Herein, we tested the hypothesis that acute ethanol treatment inhibits inflammatory, while increasing inhibitory cytokine production in human blood monocytes that, in turn, could contribute to the overall immune abnormalities seen after alcohol use. Our data show that in vitro treatment of blood monocytes with a physiologically relevant dose of alcohol (25 mM) results in significantly decreased induction of tumor necrosis factor-alpha (TNF alpha) and interleukin (IL)-1 beta by bacterial stimulation of either Gram-positive [staphylococcal enterotoxin B (SEB), 1 …


Human Monocytes, Macrophages, And Dendritic Cells: Alcohol Treatment Methods, Gyongyi Szabo, Pranoti Mandrekar Apr 2010

Human Monocytes, Macrophages, And Dendritic Cells: Alcohol Treatment Methods, Gyongyi Szabo, Pranoti Mandrekar

Gyongyi Szabo

Both acute and chronic alcohol consumption have significant immunomodulatory effects of which alterations in innate immune functions contribute to impaired antimicrobial defense and inflammatory responses. Blood monocytes, macrophages, and dendritic cells play a central role in innate immune recognition as these cells recognize pathogens, respond with inflammatory cytokine production, and induce antigen-specific T-lymphocyte activation. All of these innate immune cell functions are affected in humans by alcohol intake. Here, we summarize the different effects of acute and chronic alcohol on monocyte, macrophage, and dendritic cell functions in humans and describe methods for separation and functional evaluation of these cell types.


Human Macrophages Degrade Tryptophan Upon Induction By Interferon-Gamma, Ernst Werner, Gabriele Bitterlich, Dietmar Fuchs, Arno Hausen, Gilbert Reibnegger, Gyongyi Szabo, Manfred Dierich, Helmut Wachter Apr 2010

Human Macrophages Degrade Tryptophan Upon Induction By Interferon-Gamma, Ernst Werner, Gabriele Bitterlich, Dietmar Fuchs, Arno Hausen, Gilbert Reibnegger, Gyongyi Szabo, Manfred Dierich, Helmut Wachter

Gyongyi Szabo

Human peripheral blood mononuclear cells, monocytes-macrophages and T-cells were stimulated with human recombinant interferon-gamma, interferon-alpha and phytohemagglutinin. The culture supernatants were analyzed for tryptophan, kynurenine, 3-hydroxyanthranilic acid, anthranilic acid and neopterin by high performance liquid chromatography. Tryptophan was decreased and the four other compounds were increased in supernatants of peripheral blood mononuclear cells activated by interferon-gamma (250 U/ml), interferon-alpha (10.000 U/ml) and phytohemagglutinin (1 microgram/ml). After splitting of peripheral blood mononuclear cells by adherence, the monocytes and macrophages but not the T-cells degraded tryptophan upon stimulation by interferon-gamma in a dose dependent manner. Supernatants of phytohemagglutinin stimulated but not of …


Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo Apr 2010

Regulation Of Monocyte Interleukin-12 Production By Acute Alcohol: A Role For Inhibition By Interleukin-10, Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Gyongyi Szabo

Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, …