國家衛生研究院 NHRI:Item 3990099045/4073
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    題名: Triggering of DC migration by dengue virus stimulation of COX-2-dependent signaling cascades in vitro highlights the significance of these cascades beyond inflammation
    作者: Wu, WL;Ho, LJ;Chang, DM;Chen, CH;Lai, JH
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: A term "bone-breaking fever" is used in Chinese medicine to describe the symptoms of patients infected with dengue virus (DV). We examined the significance of the COX-prostaglandin pathway in human DC infected by DV. We show that DV infection induced the expression of COX-2 and the production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in DC, and stimulated the DNA binding of NF-κB and the kinase activity of both IκBα kinase (IKK) α and β. DV infection also activated MAPK and AP-1 signaling. Both IκBα kinase-NF-κB and MAPK-AP-1 were upstream of COX-2 activation. Our investigation into the significance of COX-2-PGE<sub>2</sub> pathway also revealed that DV infection enhances DC migration by inducing CC chemokine receptor 7 (CCR7) expression, and that blocking COX-2 or MAPK activity suppresses DV-induced DC migration. Our data also suggest that PGE<sub>2</sub> can induce CCR7 expression on DC and that antagonists of the PGE<sub>2</sub> receptors EP2 and EP4 suppress DV-induced DC migration. We further show that the increased CCR7 expression was observed in both DV-infected and bystander DC, suggesting the presence of secondary effects in inducing CCR7 expression. Collectively, this study reveals not only the pathways involved in COX-2 synthesis in DV-infected DC but also the autocrine action of PGE<sub>2</sub> on the migration of DV-infected DC.
    日期: 2009-12
    關聯: European Journal of Immunology. 2009 Dec;39(12):3413-3422.
    Link to: http://dx.doi.org/10.1002/eji.200939306
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0014-2980&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000272928300018
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=73249146831
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