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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4770-4780. Prepublished online as a Blood First Edition Paper on February 14, 2006; DOI 10.1182/blood-2005-11-4721. This Article Full Text (PDF) All Versions of this Article: 2005-11-4721v1 107/12/4770    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 Persidsky, Y. Articles by Ikezu, T. Search for Related Content PubMed PubMed Citation Articles by Persidsky, Y. Articles by Ikezu, T. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 2, 2005 Accepted January 30, 2006 Rho-mediated regulation of tight junctions during monocyte migration across blood-brain barrier in HIV-1 encephalitis (HIVE) Yuri Persidsky*, David Heilman, James Haorah, Marina Zelivyanskaya, Raisa Persidsky, Gregory A Weber, Hiroaki Shimokawa, Kozo Kaibuchi, and Tsuneya Ikezu Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Science, Higashi-ku, Fukuoka, Japan Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan * Corresponding author; email: ypersids{at}unmc.edu. The blood-brain barrier (BBB) is compromised during progressive HIV-1 infection, but how this occurs is incompletely understood. We studied the integrity of tight junctions (TJ) of brain microvascular endothelial cell (BMVEC) in vitro BBB system and in human brain tissues with HIV-1 encephalitis (HIVE). A down-regulation of TJ proteins, claudin-5 and occludin paralleled monocyte migration into the brain during HIVE. As small G-proteins (such as Rho) can play a role in BMVEC TJ assembly, an artificial BBB system explored relationship between TJ, Rho/Rho kinase (RhoK) activation and transendothelial monocyte migration. Co-culture of monocytes with endothelial cells led to Rho activation and phosphorylation of TJ proteins. Rho and RhoK inhibitors blocked migration of infected and uninfected monocytes. The RhoK inhibitor protected BBB integrity and reversed occludin/claudin-5 phosphorylation associated with monocytes migration. BMVEC transfection with constitutively active mutant of RhoK led to dislocation of occludin from the membrane and loss of BMVEC cell contacts. When dominant negative RhoK transfected BMVEC were used in BBB constructs, monocyte migration was reduced by 84%. Thus, loss of TJ integrity was associated with Rho activation caused by monocyte brain migration suggesting that Rho/RhoK activation in BMVEC could be underlying cause BBB impairment during HIVE. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Do not Rho tight junctions (or they become leaky) Michal Toborek Blood 2006 107: 4581. [Full Text] [PDF] This article has been cited by other articles: R. Potula and Y. Persidsky Adding Fuel to the Fire: Methamphetamine Enhances HIV Infection Am. J. Pathol., June 1, 2008; 172(6): 1467 - 1470. [Abstract] [Full Text] [PDF] S. H. Ramirez, D. Heilman, B. Morsey, R. Potula, J. Haorah, and Y. Persidsky Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) Suppresses Rho GTPases in Human Brain Microvascular Endothelial Cells and Inhibits Adhesion and Transendothelial Migration of HIV-1 Infected Monocytes J. Immunol., February 1, 2008; 180(3): 1854 - 1865. [Abstract] [Full Text] [PDF] M. Yamamoto, S. H. Ramirez, S. Sato, T. Kiyota, R. L. Cerny, K. Kaibuchi, Y. Persidsky, and T. Ikezu Phosphorylation of Claudin-5 and Occludin by Rho Kinase in Brain Endothelial Cells Am. J. Pathol., February 1, 2008; 172(2): 521 - 533. [Abstract] [Full Text] [PDF] E. A. Eugenin and J. W. Berman Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes J. Neurosci., November 21, 2007; 27(47): 12844 - 12850. [Abstract] [Full Text] [PDF] G. Schreibelt, G. Kooij, A. Reijerkerk, R. van Doorn, S. I. Gringhuis, S. van der Pol, B. B. Weksler, I. A. Romero, P.-O. Couraud, J. Piontek, et al. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling FASEB J, November 1, 2007; 21(13): 3666 - 3676. [Abstract] [Full Text] [PDF] P. V. Afonso, S. Ozden, M.-C. Prevost, C. Schmitt, D. Seilhean, B. Weksler, P.-O. Couraud, A. Gessain, I. A. Romero, and P.-E. Ceccaldi Human Blood-Brain Barrier Disruption by Retroviral-Infected Lymphocytes: Role of Myosin Light Chain Kinase in Endothelial Tight-Junction Disorganization J. Immunol., August 15, 2007; 179(4): 2576 - 2583. [Abstract] [Full Text] [PDF] F. Wegmann, B. Petri, A. G. Khandoga, C. Moser, A. Khandoga, S. Volkery, H. Li, I. Nasdala, O. Brandau, R. Fassler, et al. ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability J. Exp. Med., July 10, 2006; 203(7): 1671 - 1677. [Abstract] [Full Text] [PDF]

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