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.
Date:
2009-12
Relation:
European Journal of Immunology. 2009 Dec;39(12):3413-3422.
