Cross-talk between STAT1 and PI3K/AKT signaling in HIV-1-induced blood-brain barrier dysfunction: role of CCR5 and implications for viral neuropathogenesis.
Cross-talk between STAT1 and PI3K/AKT signaling in HIV-1-induced blood-brain barrier dysfunction: role of CCR5 and implications for viral neuropathogenesis.
复制标题
DOI：
10.1002/jnr.22458
复制
发表时间：
2010-11-01
影响因子：
4.2
通讯作者：
Kanmogne, Georgette D.
中科院分区：
文献类型：
--
作者：
Yang, Bo;Singh, Sangya;Bressani, Rafael;Kanmogne, Georgette D.
How neuroinflammation affects signaling pathways leading to human blood–brain barrier (BBB) dysfunction during HIV-1 infection is incompletely understood. We previously demonstrated that signal transducers and activators of transcription-1 (STAT1) signaling is involved in HIV-1 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-1-induced endothelial dysfunction. We show that HIV-1 activation of STAT1 and STAT3 in human brain microvascular endothelial cells (HBMEC) is associated with induction of promoter activity of the interferon-stimulated response element (ISRE)/interferon-γ-activated sequence (GAS). The STAT1 inhibitor fludarabine diminished HIV-1-induced ISRE/GAS promoter activity. CCR5 neutralizing antibodies and the phosphoinositide-3-kinase (PI3K) inhibitor LY-294002 diminished HIV-1-induced phosphorylation of STAT1 and STAT3, significantly diminished HIV-1-induced ISRE/GAS promoter activity, and diminished virus-induced monocyte adhesion and transendothelial migration. HIV-1 infection did not phosphorylate janus kinases but induced activation of the phosphoinositide-dependent kinase-1 (PDK1) and the serine-threonine protein kinase AKT, both downstream effectors of PI3K. CCR5 antibodies also diminished virus-induced phosphorylation of PDK1 and AKT. These results suggest that the chemokine receptor CCR5 is partially involved in HIV-1 binding to HBMEC and show cross-talk between STAT1 and PI3K pathways in HIV-1-induced BBB dysfunction.
登录
查看更多内容
影响因子：
3.8
作者：
Irlbeck, David M.;Amrine-Madsen, Heather;Demarest, James F.
通讯作者：
Demarest, James F.
影响因子：
6
作者：
Dallasta, LM;Pisarov, LA;Achim, CL
通讯作者：
Achim, CL
影响因子：
5.5
作者：
Lee, C;Tomkowicz, B;Coliman, RG
通讯作者：
Coliman, RG
影响因子：
5.3
作者：
Eugenin, EA;Osiecki, K;Berman, JW
通讯作者：
Berman, JW
影响因子：
8
作者：
Decker, T;Kovarik, P
通讯作者：
Kovarik, P