Activation of JNK1/2 and p38 MAPK signaling pathways promotes enterovirus 71 infection in immature dendritic cells
- Equal contributors
1 Department of Clinical Laboratory, the Third Affiliated Hospital of Suzhou University, No. 185 Juqian street, Changzhou, Jiangsu 213003, P. R. China
2 Department of Oncology Laboratory, the Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu 213003, China
BMC Microbiology 2014, 14:147 doi:10.1186/1471-2180-14-147Published: 7 June 2014
c-Jun NH2-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38 MAPK) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. However, little is known about JNK1/2 and p38 MAPK signaling pathways in enterovirus 71 (EV71)-infected immature dendritic cells (iDCs). Thus, iDCs were induced from peripheral blood mononuclear cells (PBMC) and performed to explore the expressions and phosphorylation of molecules in the two signaling pathways as well as secretions of inflammatory cytokines and interferons during EV71 replication.
We showed that EV71 infection could activate both JNK1/2 and p38 MAPK in iDCs and phosphorylate their downstream transcription factors c-Fos and c-Jun, which further promoted the production of IL-2, IL-6, IL-10, and TNF-α. Moreover, EV71 infection also increased the release of IFN-β and IL-12 p40. Pretreatment of iDCs with SP600125 and SB203580 (20 μM) could severely impair viral replication and its induced phosphorylation of JNK1/2,p38 MAPK, c-Fos and c-Jun. In addition, treatment of EV71-infected iDCs with SP600125 and SB203580 could inhibit secretions of IL-6, IL-10 and TNF-α.
JNK1/2 and p38 MAPK signaling pathways are beneficial to EV71 infection and positively regulate secretions of inflammatory cytokines in iDCs.