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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2062-2072. Prepublished online as a Blood First Edition Paper on November 14, 2007; DOI 10.1182/blood-2007-05-091207. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-091207v1 111/4/2062    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Anathbandhu, C. Articles by Kanmogne, G. D Search for Related Content PubMed PubMed Citation Articles by Anathbandhu, C. Articles by Kanmogne, G. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 18, 2007 Accepted November 1, 2007 STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier Chaudhuri Anathbandhu, Bo Yang, Howard E. Gendelman, Yuri Persidsky, and Georgette D Kanmogne* Center for Neurovirology & Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, United States Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States * Corresponding author; email: gkanmogne{at}unmc.edu. The relationship between neuroinflammation, blood-brain barrier (BBB) dysfunction, and progressive HIV-1 infection as they affect the onset and development of neuroAIDS is incompletely understood. One possible link is signal transducers and activators of transcription (STAT) pathways. These respond to pro-inflammatory and regulatory factors and could affect neuroinflammatory responses induced from infected cells and disease affected brain tissue. Our previous works demonstrated that HIV-1 activate pro-inflammatory and interferon-alpha-inducible genes in human brain microvascular endothelial cells (HBMEC) and that these genes are linked to the janus kinase (JAK)/STAT pathway. We now demonstrate that HIV-1 activates STAT1, induces IL-6 expression, and diminishes expression of claudin-5, ZO-1, and ZO-2 in HBMEC. The STAT1 inhibitor, fludarabine, blocked HIV-1-induced IL-6, diminished HIV-1-induced claudin-5 and ZO-1 downregulation, and blocked HIV-1- and IL-6-induced monocyte migration across a BBB model. Enhanced expression and activation of STAT1 and decreased claudin-5 was observed in microvessels from autopsy brains of patients with HIV-1-associated dementia. These data support the notion that STAT1 plays an integral role in HIV-1-induced BBB damage and is relevant to viral neuropathogenesis. Inhibition of STAT1 activation could provide a unique therapeutic strategy to attenuate HIV-1-induced BBB compromise and as such improve clinical outcomes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Nilsberth, L. Elander, N. Hamzic, M. Norell, J. Lonn, L. Engstrom, and A. Blomqvist The Role of Interleukin-6 in Lipopolysaccharide-Induced Fever by Mechanisms Independent of Prostaglandin E2 Endocrinology, April 1, 2009; 150(4): 1850 - 1860. [Abstract] [Full Text] [PDF]

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