Welcome to the Homepage of
Dr. Bryan L. Spangelo

Professor of Biochemistry

Department of Chemistry
University of Nevada, Las Vegas
4505 Maryland Parkway
Box 454003
Las Vegas, NV 89154-4003
Telephone: (702) 895-3797
Fax: (702) 895-4072
Email: bryan.spangelo@unlv.edu

Education

Major Teaching Responsibilities:

Research Interests

The cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) are proinflammatory mediators present in the central nervous system. Excessive glial cytokine production contributes to neurodegenerative processes such as Alzheimer’s Disease (AD). A mechanism by which IL-1 activates glia is unknown, as are the effects of inhibitory neurotransmitters on the regulation of IL-1 signaling. We have demonstrated that IL-1 stimulates IL-6 release from C6 astrocytoma cells. Inhibition of p38 mitogen-activated protein kinase (MAPK) compromises IL-1 action in C6 cells, as does the inhibitory neurotransmitter gama-aminobutyric acid (GABA). We are delineating a p38-driven pathway underlying IL-1 action in C6 cells and primary rat astrocytes, and identifying potential post-receptor mechanisms through which inhibitory transmitters interfere with IL-1-driven signaling. Our primary hypotheses are that p38 is essential for IL-1-stimulated IL-6 release form astroglial cells, and that GABA abrogates this by blockade of one or more MAPK pathways. We predict that inhibitory neurotransmitters will block activation of these kinases, thus preventing subsequent cytokine production and neuronal cell death. Our studies are the very first to investigate the effects of inhibitory neurotransmitters on cytokine activation processes in astrocytes.

Our results have revealed probable cellular mechanisms by which GABA restricts glial elaboration of inflammatory cytokines. Though once considered protective cellular elements in the CNS, activated astrocytes and microglia deliver lethal, neurotoxic insults during AD. Understanding molecular mechanisms by which neurotransmitters can prevent such toxic glial activation will provide new strategies for pharmacological abrogation of glial-mediated neuronal injury.

Research Support

Our current studies are supported by the National Institute of Neurologoical Disorders and Stroke (1R15 NS051198-01A1).

Selected Publications

Spangelo, B.L. , deHoll, P.D., Kalabay, L., Bond, B.R., and Arnaud, P. Neurointermediate pituitary lobe cells synthesize and release interleukin-6 in vitro: effects of lipopolysaccharide and interleukin-1ß. Endocrinology 135:556-563, 1994.

Spangelo, B.L. , and Jarvis, W.D. Lysophosphatidylcholine stimulates interleukin-6 release from rat anterior pituitary cells in vitro. Endocrinology 137:4419-4426, 1996.

Tijerina, M., Gorospe, W.C., Bowman, K.-L., Badamchian, M., Goldstein, A.L., and Spangelo, B.L. A novel thymosin peptide stimulates interleukin-6 release from rat C6 glioma cells in vitro. NeuroImmunoModulation 4:163-170, 1997.

Spangelo, B.L., Farrimond, D.D., Thapa, M., Bulathsinghala, C.M., Bowman, K.-L., Sareh, A., Hughes, F.M.Jr., Goldstein, A.L., and Badamchian, M. Thymosin fraction 5 inhibits the proliferation of the rat neuroendocrine MMQ pituitary adenoma and C6 glioma cell lines in vitro. Endocrinology 139:2155-2162, 1998.

Zumwalt, J., Thunstrom, B., and Spangelo, B.L. Interleukin-1ß and catecholamines synergistically stimulate interleukin-6 release from rat C6 glioma cells in vitro: a potential role for lysophosphatidylcholine. Endocrinology 140:888-896, 1999.

Spangelo, B.L. , Farrimond, D.D., Pompilius, M., and Bowman, K. Interleukin-1 b and thymic peptide regulation of pituitary and glial cell cytokine expression and cellular proliferation. The New York Academy of Sciences, volume 917, 2000, pp. 597-607.

Spangelo, B.L. , Horrell, D.S., Goodwin, A.L., Shroff, S., and Jarvis W.D. Somatostatin and g -aminobutyric acid inhibit interleukin-1 b -stimulated release of interleukin-6 from rat C6 glioma cells. NeuroImmunoModulation 11:332-340, 2004.

Spangelo, B.L ., Pompilius, M., Farrimond, D.D., Stevens, N., Nieva, R., Shroff, S., Badamchian, M., Johnson, C.R., and Jarvis, W.D. Presence of a peptide component of thymosin fraction-5manifesting discrete cytostatic properties in HL-60 human promyelocytic leukemia cells. International Immunopharmacology 5:1317-1329, 2005.

Roach, J., Aguinaldo, G.T., Jonnalagadda, K., Hughes, F.M.Jr., and Spangelo, B.L.  g-Aminobutyric acid inhibits synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells. Neuroimmunomodulation 15:117-124, 2008.

Spangelo, B.L., Roach, J.D., Hadi, F., Damavandy, A.A., Plieskatt, J., and Badamchian, M.  Thymosin fraction-5 possesses antiproliferative properties in HL-60 human promyelocytic leukemia cells: characterization of an active peptide.  Annals of the New York Academy of Sciences 1112:305-316, 2007