TNF-alpha mediates pseudorabies virus-induced apoptosis via the activation of p38 MAPK and JNK/SAPK signaling.
PRV infection causes apoptosis in vitro and in vivo. However, the significance of PRV-induced apoptosis and its signaling pathways is still unknown. This work investigates the role of MAPK pathways in mediating PRV-induced apoptosis. Flow cytometry, apoptosis ELISA and western blotting using antibodies against cleaved caspase-3, -6 and PARP demonstrated that PRV induces apoptosis in a time- and dose-dependent manner. p38 and JNK/SAPK inhibitors significantly protected cells from PRV-induced apoptosis. Inhibitor treatment did not affect Us3a gene transcription and progeny virus production. Western blotting revealed that PRV activates p38 and JNK/SAPK signaling. Inhibition of NF-kappaB had no effect on PRV-mediated apoptosis. Non-replicative PRV failed to activate p38 and JNK/SAPK or induce apoptosis. PRV infection increases TNF-alpha transcription, translation and secretion, as well as TNF-alpha receptor expression. Inhibition of p38 and JNK/SAPK reduced PRV-induced TNF-alpha up-regulation. Neutralization assay confirmed that TNF-alpha is a key mediator involved in PRV-induced apoptosis.
Yeh
Ching-Ju
CJ
Graduate Institute and Department of Life Science, Tzu-Chi University, Hualien, Taiwan.
Lin
Ping-Yuan
PY
Liao
Ming-Huei
MH
Liu
Hung-Jen
HJ
Lee
Jeng-Woei
JW
Chiu
Shu-Jun
SJ
Hsu
Hsue-Yin
HY
Shih
Wen-Ling
WL
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011557:Pseudorabies / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014709:Vero Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000906:Antibodies; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases