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The Journal of Neuroscience, August 1, 1999, 19(15):6468-6474

Gp-41-Mediated Astrocyte Inducible Nitric Oxide Synthase mRNA Expression: Involvement of Interleukin-1 Production by Microglia

Shuxian Hu, Humaira Ali, Wen S. Sheng, Laura C. Ehrlich, Phillip K. Peterson, and Chun C. Chao

Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation and the University of Minnesota Medical School, Minneapolis, Minnesota 55404

Mechanisms underlying human immunodeficiency virus-1 encephalopathy are not completely known; however, recent studies suggest that the viral protein gp41 may be neurotoxic via activation of inducible nitric oxide synthase (iNOS) in glial cells. In the present study, we investigated the NO-generating activity of primary human fetal astrocytes in response to gp41 and the relationship to microglial cell production of interleukin-1 (IL-1). Gp41 failed to trigger iNOS mRNA expression in highly enriched (>99%) astrocyte or microglial cell cultures. However, gp41-treated microglia released a factor(s) that triggered iNOS mRNA expression and NO production in astrocytes. Because IL-1 receptor antagonist protein blocked gp41-induced NO production, a pivotal role was suggested for microglial cell IL-1 production in astrocyte iNOS expression. Also, gp41 induced IL-1 mRNA expression and IL-1 production in microglial cell but not astrocyte cultures. Using specific inhibitors, we found that gp41-induced IL-1 production in microglia was mediated via a signaling pathway involving protein-tyrosine kinase. These data support the hypothesis that gp41 induces astrocyte NO production indirectly by triggering upregulation of microglial cell IL-1 expression.

Key words: astrocytes; cytokines; human immunodeficiency virus-1; interleukin-1; microglia; nitric oxide; nitric oxide synthase; protein-tyrosine kinase

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19156468-07$05.00/0

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				X. Liu, M. Jana, S. Dasgupta, S. Koka, J. He, C. Wood, and K. Pahan Human Immunodeficiency Virus Type 1 (HIV-1) Tat Induces Nitric-oxide Synthase in Human Astroglia J. Biol. Chem., October 11, 2002; 277(42): 39312 - 39319. [Abstract] [Full Text] [PDF]

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