Involvement of the Akt/NF-κB pathways in the HTNV-mediated increase of IL-6, CCL5, ICAM-1, and VCAM-1 in HUVECs.
BACKGROUND
Hantaan virus (HTNV) infection causes a severe form of HFRS(hemorrhagic fever with renal syndrome)in Asia. Although HTNV has been isolated for nearly forty years, the pathogenesis of HFRS is still unknown, and little is known regarding the signaling pathway that is activated by the virus.


RESULTS
Cardamonin was selected as a NF-κB inhibitor, and indirect immunofluorescence assays were used to detect the effect of cardamonin on HTNV-infected HUVECs. The effect of cardamonin on the HTNV-induced phosphorylation of Akt and DNA-binding activity of NF-κB were determined using Western blot analysis and electrophoretic mobility shift assays (EMSAs), respectively. Then, flow cytometric and quantitative real-time PCR analyses were performed to quantify the expression levels of the adhesion molecules ICAM-1 and VCAM-1, and the concentrations of IL-6, IL-8, and CCL5 in HUVEC supernatants were examined using ELISA. The results showed that cardamonin did not effect the proliferation of HUVECs or the replication of HTNV in HUVECs. Instead, cardamonin inhibited the phosphorylation of Akt and nuclear transduction of NF-κB and further reduced the expression of the adhesion molecules ICAM-1 and VCAM-1 in HTNV-infected HUVECs. Cardamonin also inhibited the secretion of IL-6 and CCL5, but not IL-8.


CONCLUSIONS
HTNV replication may not be dependent upon the ability of the virus to activate NF-κB in HUVECs. The Akt/NF-κB pathways may be involved in the pathogenesis of HFRS; therefore, cardamonin may serve as a potential beneficial agent for HFRS therapy.
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Haitao
H
Yu
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Wei
W
Jiang
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Hong
H
Du
Department of Physiology, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Yuan
Y
Xing
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Guangzhen
G
Bai
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Ye
Y
Zhang
Department of Infectious Diseases, Shaanxi Provincial People's Hospital,Xi'an, Shaanxi Province, China.
Yu
Y
Li
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Hong
H
Jiang
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Ying
Y
Zhang
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Jiuping
J
Wang
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Pingzhong
P
Wang
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Xuefan
X
Bai
D047188:Chalcones / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000378:metabolism*; D018063:Hantaan virus; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D047188:Chalcones; D018946:Chemokine CCL5; D015850:Interleukin-6; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; C436747:cardamonin