{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T08:13:24Z","timestamp":1773303204719,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T00:00:00Z","timestamp":1277078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>How neuroinflammation affects signaling pathways leading to human blood\u2013brain barrier (BBB) dysfunction during HIV\u20101 infection is incompletely understood. We previously demonstrated that signal transducers and activators of transcription\u20101 (STAT1) signaling is involved in HIV\u20101 induced BBB damage and is relevant to viral neuropathogenesis. The objective of this study was to delineate the signaling pathways upstream and downstream of STAT1 involved in HIV\u20101\u2010induced endothelial dysfunction. We show that HIV\u20101 activation of STAT1 and STAT3 in human brain microvascular endothelial cells (HBMEC) is associated with induction of promoter activity of the interferon\u2010stimulated response element (ISRE)\/interferon\u2010\u03b3\u2010activated sequence (GAS). The STAT1 inhibitor fludarabine diminished HIV\u20101\u2010induced ISRE\/GAS promoter activity. CCR5 neutralizing antibodies and the phosphoinositide\u20103\u2010kinase (PI3K) inhibitor LY\u2010294002 diminished HIV\u20101\u2010induced phosphorylation of STAT1 and STAT3, significantly diminished HIV\u20101\u2010induced ISRE\/GAS promoter activity, and diminished virus\u2010induced monocyte adhesion and transendothelial migration. HIV\u20101 infection did not phosphorylate janus kinases but induced activation of the phosphoinositide\u2010dependent kinase\u20101 (PDK1) and the serine\u2010threonine protein kinase AKT, both downstream effectors of PI3K. CCR5 antibodies also diminished virus\u2010induced phosphorylation ofPDK1 and AKT. These results suggest that the chemokine receptor CCR5 is partially involved in HIV\u20101 binding to HBMEC and show cross\u2010talk between STAT1 and PI3K pathways in HIV\u20101\u2010induced BBB dysfunction. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22458","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T17:31:36Z","timestamp":1277141496000},"page":"3090-3101","source":"Crossref","is-referenced-by-count":33,"title":["Cross\u2010talk between STAT1 and PI3K\/AKT signaling in HIV\u20101\u2010induced blood\u2013brain barrier dysfunction: Role of CCR5 and implications for viral 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