The role of ERK1/2 signaling pathway in Nef protein upregulation of the expression of the intercellular adhesion molecule 1 in endothelial cells.
Human immunodeficiency virus (HIV)-infected patients have increased rates of atherosclerotic cardiovascular diseases because the highly active antiretroviral therapy (HAART) decreased the morbidity and mortality of the disease. Endothelial dysfunction is possibly the most plausible link between HIV infection and related expression of cell adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on the endothelial cells. HIV-1 accessory protein negative regulate factor (Nef) has been shown to be very important for high virus replication and disease progression. Nef could upregulate the expression of ICAM-1 in the pathogenesis of HIV infection. Here, we provide evidence that the HIV-1 Nef can transcriptionally induce the expression of ICAM-1 in stable expressed Nef vascular endothelial cells. Nef-induced ICAM-1 upregulation requires the activation of the downstream kinase extracellular signal-regulated kinase (ERK). Flow cytometry (FCM) results showed that the percentage of ICAM-1 positive cells in Nef-expressed cells and control cells was (35.3% +/- 2.2%) and (12.5% +/- 0.8%), respectively (P < .01). Furthermore, inhibition of Nef activity by ERK mitogen-activated protein kinase (MAPK) inhibitor effectively blocked ICAM-1 upregulation, suggesting that ERK MAPK activation is an important initiating event in Nef-mediated ICAM-1 expression in Nef-expressed cells. These data demonstrate an important signaling event of Nef in HIV-1 pathogenesis.
Fan
Yang
Y
Institute of Molecular Biology of Three Gorges University, Yichang, Hubei Province, China.
Liu
Chaoqi
C
Qin
Xiaolin
X
Wang
Yanlin
Y
Han
Yu
Y
Zhou
Yongqin
Y
D015153:Blotting, Western; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D015693:Gene Products, nef / Q000502:physiology; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D019169:Jurkat Cells / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D018799:Intercellular Adhesion Molecule-1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3