Enterovirus 71-induced iNOS and VCAM-1 Expressionvia MAPKs and PI3-K/Akt in Rat Vascular Smooth Muscle Cells

Autor: Wei-Hsuan Tung, 董維軒
Rok vydání: 2005
Druh dokumentu: 學位論文 ; thesis
Popis: 93
Enterovirus 71 (EV71) is a widespread virus that causes severe and fatal diseases in patients, including circulation failure. The blood vessel will be damaged first, and produced necrosis and inflammation, this phenomenon is called vasculitis. Vasculitis is an inflammatory disorder mediated by vascular cell adhesion molecule-1 (VCAM-1) or nitric oxide. In previous study, the value of plasma levels of VCAM-1 and NO in the pathogenesis and prognosis was investigated in body with virus infections of varying severity. But the mechanisms underlying EV71-initiated intracellular signaling pathways to influence host cell functions remain unknown. In this study, we have identified EV71-indued PDGFR, Akt, ERK, p38, NF-B activation and iNOS, VCAM-1 expression in a time- and viral dose-dependent manner. Treatment of RV-SMCs with EV71 stimulated phosphorylation of PDGFR, Akt, ERK, and p38which was attenuated by AG1296, LY294002, Wortmannin, U0126, and SB202190, respectively. The PDGFR inhibitor (AG1296), PI3-K inhibitor (LY294002, Wortmannin), and ERK inhibitor (U0126) inhibited EV-71-induced iNOS expression. And the PDGFR inhibitor (AG1296), PI3-K inhibitor (LY294002, Wortmannin), p38 inhibitor (SB202190), and JNK inhibitor (SP600125) inhibited EV-71-induced VCAM-1 expression. Furthermore, iNOS and VCAM-1 expression induced by EV71 was significantly attenuated by a selective NF-B inhibitor (Helenalin). Consistently, EV71-stimulated translocation of NF-B into the nucleus and degradation of IB-α was blocked by Helenalin, AG1296, SB202190, SP600125, LY294002, and Wortmannin. These findings suggest that EV71 interacting through adhesion receptors initiates PDGFR-, PI3-K/Akt, p38-, and NF-B-dependent signaling pathways that mediate VCAM-1 expression in RV-SMCs, but not via p42/p44 MAPK. In addition, EV71 interacting through adhesion receptors initiates PDGFR-, PI3-K/Akt, p42/p44 MAPK-, and NF-κB-dependent signaling pathways that mediate iNOS expression in RV-SMCs.
Databáze: Networked Digital Library of Theses & Dissertations
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