title: Rosiglitazone suppresses HIV-1 Tat-induced vascular inflammation via Akt signaling.
abstract: Peroxisome proliferator-activated receptor gamma (PPARƔ) contributes to human immunodeficiency virus (HIV)-1-induced dysfunction of brain endothelial cells. The aim of the present study was to evaluate the protection mechanism of PPARƔ against Tat-induced responses of adhesion molecules. We measured the protein expressions of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in human brain microvascular endothelial cells (hCMEC/D3) and C57BL/6J mouse brain microvessels with Western blotting and immunofluorescent labeling. The mRNA levels of ICAM-1 and VCAM-1 were determined by real-time reverse-transcriptase polymerase chain reaction. HIV-1 Tat induced overexpression of ICAM-1 but not VCAM-1 in both hCMEC/D3 and brain microvessels, this response was attenuated by treatment with the PPARƔ agonist rosiglitazone. Tat-mediated upregulation of ICAM-1 and VCAM-1 levels were abolished by the addition of PPARƔ antagonist GW9662 and the Akt inhibitor KP3721, indicating that Akt signaling is involved in the PPARƔ-mediated protection of Tat-induced adhesion molecule upregulation. These results show that Akt signaling plays a key role in PPARƔ's vascular inflammatory effects that contribute to blood-brain barrier damage.
authors.affiliation: Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.forename: Xuean
authors.initials: X
authors.lastname: Mo
authors.forename: Xianghong
authors.initials: X
authors.lastname: Wu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Luo
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000166:cytology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt