EV71 induces VCAM-1 expression via PDGF receptor, PI3-K/Akt, p38 MAPK, JNK and NF-kappaB in vascular smooth muscle cells.

Abstract

Enterovirus 71 (EV71) is a widespread virus that causes severe and fatal diseases in patients, including circulation failure. The mechanisms underlying EV71-initiated intracellular signaling pathways to influence host cell functions remain unknown. In this study, we identified a requirement for PDGFR, PI3-K/Akt, p38 MAPK, JNK, and NF-kappaB in the regulation of VCAM-1 expression by rat vascular smooth muscle cells (VSMCs) in response to viral infection. EV71 induced VCAM-1 expression in a time- and viral concentration-dependent manner. Infection of VSMCs with EV71 stimulated VCAM-1 expression and phosphorylation of PDGFR, Akt, and p38 MAPK which were attenuated by AG1296, wortmannin, and SB202190, respectively. The phosphorylation of JNK stimulated by EV71 was not detected under present conditions. In contrast, JNK inhibitor SP600125 inhibited EV71-induced VCAM-1 expression. Furthermore, VCAM-1 expression induced by EV71 was significantly attenuated by a selective NF-kappaB inhibitor (helenalin). Consistently, EV71-stimulated translocation of NF-kappaB into the nucleus and degradation of IkappaB-alpha as well as VCAM-1 mRNA expression was blocked by helenalin, AG1296, SB202190, SP600125, wortmannin, and LY294002. Moreover, the involvement of p38 MAPK, PI3-K/Akt, and NF-kappaB in EV71-induced VCAM-1 expression was reveled by that transfection with dominant negative plasmids of p38 MAPK, p85, Akt, NIK, IKK-alpha, and IKK-beta attenuated these responses. These findings suggest that in VSMCs, EV71-induced VCAM-1 expression was mediated through activation of PDGFR, PI3-K/Akt, p38 MAPK, JNK, and NF-kappaB pathways.

• Authors: Wei-Hsuan Tung, Chi-Chin Sun, Hsi-Lung Hsieh, Shyi-Wu Wang, Jim-Tong Horng, Chuen-Mao Yang
• Journal: Cellular signalling (Cell Signal) Vol. 19 Issue 10 Pg. 2127-37 (Oct 2007) ISSN: 0898-6568 [Print] England
• PMID: 17669626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Vascular Cell Adhesion Molecule-1
• Phosphatidylinositol 3-Kinases
• Receptors, Platelet-Derived Growth Factor
• Proto-Oncogene Proteins c-akt
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Cell Adhesion
• Cells, Cultured
• Enterovirus (physiology)
• Gene Expression
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Muscle, Smooth, Vascular (enzymology, metabolism, virology)
• NF-kappa B (metabolism)
• Neutrophils (physiology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Platelet-Derived Growth Factor (metabolism)
• Signal Transduction
• Vascular Cell Adhesion Molecule-1 (biosynthesis, genetics)
• p38 Mitogen-Activated Protein Kinases (metabolism)