475. NOREPINEPHRINE MODULATES HUMAN DENDRITIC CELL ACTIVATION BY ALTERING CYTOKINE RELEASE.

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Goyarts¹, E., Matsui¹, M., Mammone¹, T., Bender², A.M., Wagner³, J.A., Maes¹, D., and Granstein², R.D. ¹Clinique Laboratories, Melville, NY, USA; ²Department of Dermatology, Weill Medical College of Cornell University, New York, NY, USA; ³Department of Neurology & Neuroscience, Weill Medical College of Cornell University, New York, NY, USA. Experimental Dermatology, 17, 188-196, (2007).

Summary:
This study by researchers at Weill Medical College of Cornell University and Clinique Laboratories demonstrated how MatTek’s Human Dendritic Cells can be used to observe the effect of a specific compound (norepinephrine) on the cytokine expression of cells that are central to the immune response in human skin.

Norepinephrine (NE) can modulate dendritic cell (DC) activation in animal models, but the response of human DC to norepinephrine and other response modifiers is as yet not completely understood.

Here researchers from Weill Medical College of Cornell University and Clinique Laboratories report the effect of norepinephrine on the cytokine response of a mixed population of human DC cells to extracellular stimuli.

These cells were obtained by differentiating human cord blood CD34+ precursor cells (Human Dendritic Cells, MatTek Corp.). Norepinephrine inhibited the lipopolysaccharide (LPS)-stimulated production of interleukin (IL)-23, IL-12 p40, tumor necrosis factor (TNF)-alpha and IL-6 whereas the expression of IL-10 was not significantly affected. Thus, human cord blood-derived DC respond to NE in a manner similar to mouse Langerhans cells (LC).

Furthermore, forskolin also inhibited the LPS-induced levels of TNF-alpha, IL-12 p40, IL-23 p19 and IL-6, supporting the hypothesis that the effects of norepinephrine are mediated by cAMP. Data from experiments using inhibitors of adrenergic receptors suggest that norepinephrine acts through beta-adrenergic receptors.

As IL-23 promotes the differentiation of CD4+ T cells required for T_H1-mediated immunity, we suggest that norepinephrine decreases the differentiation of CD4+ T cells needed for T_H1-mediated contact hypersensitivity and that norepinephrine is a candidate regulator of human DC functions in the skin.

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Applications: Cytokine expression/analysis, Immunological research

Keywords: Adenylate cyclase, Adrenergic receptors, Alpha-adrenergic, Beta-adrenergic receptors, Cytokine release, DC-100, Dendritic cells (DC), Human dendritic cell activation, IL-10, IL-12 (p40), IL-23, IL-6, Interleukin, Receptors, TNF-a, Tumor necrosis factor alpha

Materials Tested: Forskolin, Lipopolysaccharide (LPS), Norepinephrine, Propranolol hydrochloride, Yohimbine hydrochloride

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