Enterovirus 71 induces COX-2 expression via MAPKs, NF-κB, and AP-1 in SK–N–SH cells: role of PGE2 in viral replication

WH Tung, HL Hsieh, CM Yang - Cellular signalling, 2010 - Elsevier
WH Tung, HL Hsieh, CM Yang
Cellular signalling, 2010Elsevier
The enterovirus 71 (EV71) causes severe neurological diseases that were mediated through
cyclooxygenase-2 (COX-2) expression in brain. However, the mechanisms underlying EV71-
initiated intracellular signaling pathways leading to COX-2 expression remain unknown in
neurons. Here we report that exposure of SK–N–SH cells to EV71 increased COX-2
expression and PGE2 generation in a time-and virus titer-dependent manner, revealed by
Western blot, real-time PCR, and PGE2 analyses. These EV71-induced responses were …
The enterovirus 71 (EV71) causes severe neurological diseases that were mediated through cyclooxygenase-2 (COX-2) expression in brain. However, the mechanisms underlying EV71-initiated intracellular signaling pathways leading to COX-2 expression remain unknown in neurons. Here we report that exposure of SK–N–SH cells to EV71 increased COX-2 expression and PGE2 generation in a time- and virus titer-dependent manner, revealed by Western blot, real-time PCR, and PGE2 analyses. These EV71-induced responses were mediated through activation of p42/p44 MAPK, p38 MAPK, JNK, NF-κB, and AP-1, revealed by using selective pharmacological inhibitors or transfection with respective siRNAs. Consistently, EV71-stimulated translocation of NF-κB into the nucleus and degradation of IκBα in the cytosol was blocked by pretreatment with the selective inhibitors of MEK1/2 (U0126) and NF-κB (Bay11-7085), respectively, suggesting that MEK1/2-p42/p44 MAPK cascade linking to NF-κB was involved in COX-2 expression. In addition, EV71-induced AP-1 subunits (c-jun and c-fos mRNA) expression was also attenuated by pretreatment with a selective JNK inhibitor SP600125, suggesting that JNK cascade linking to AP-1 was involved in COX-2 expression induced by EV71. These findings suggested that up-regulation of COX-2 associated with the release of PGE2 from EV71-infected SK–N–SH cells which was mediated through activation of p38 MAPK, JNK, p42/p44 MAPK, NF-κB, and AP-1 pathways.
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