BK-induced COX-2 expression via PKC-δ-dependent activation of p42/p44 MAPK and NF-κB in astrocytes

Bradykinin Enhances AMPA and NMDA Receptor Activity in Spinal Cord Dorsal Horn Neurons by Activating Multiple Kinases to Produce Pain Hypersensitivity

“…Mice with a null mutation of the B 2 BK receptor also have reduced secondary mechanical allodynia in the capsaicin model (Wang et al, 2005). Interestingly, bradykinin via B 2 activates ERK in several other cells Hsieh et al, 2007;Yu et al, 2007). PKC activates Raf and PKA Rap1, and thereby B-Raf (Gutkind, 2000).…”

“…Both Raf and B-Raf can activate MEK, which in turn activates ERK (Gutkind, 2000). Bradykinin activation of PKC leads to an activation of ERK in astrocytes (Hsieh et al, 2007).…”

Epidermal growth factor-dependent cyclooxygenase-2 induction in gliomas requires protein kinase C-δ

“…Iwabu et al (2004) found that EGFR-dependent activation of phospholipase C-g contributes to PKC-d activation in mouse fibroblasts. PKC-d has also been reported to activate both p38-MAPK and ERK1/2 with Hsieh et al (2007) finding that PKC-d regulates bradykinin-induced COX-2 expression through sequential activation of ERK1/2 and NF-kB in astrocytes and Park et al (2007) reporting that acrolein-induced COX-2 expression requires the sequential activation of PKC-d, p38-MAPK and cAMP response element binding protein in human umbilical vein endothelial cells. These reports show that in certain cells, PKC-d can act upstream of p38-MAPK and ERK1/2 with subsequent induction of COX-2 expression.…”

“…In addition, although c-Jun N-terminal kinase (JNK) has not been specifically associated with EGFinduced COX-2 expression, this member of the MAPK family has been reported to regulate COX-2 expression in certain setting (Guan et al, 1998;Subbaramaiah et al, 1998). Because PKC-d has been reported to regulate COX-2 expression by acting upstream of p38-MAPK and ERK1/2 in some systems (Hsieh et al, 2007;Park et al, 2007), we pretreated SF767 cells with various PKC inhibitors, including BIS, Che, GO and Rott, prior to EGF stimulation and determined whether EGFinduced activation of p38-MAPK and ERK1/2 was affected. By immunoblot analysis, EGF-induced phosphorylation of p38-MAPK and ERK1/2 was unaffected by PKC inhibition, suggesting that they are not downstream targets of PKC-d in our system (Figure 2a, upper four panels).…”

“…Moreover, increased COX-2 expression is an independent-negative prognostic factor in malignant gliomas (Shono et al, 2001). Because PKC can regulate COX-2 expression in certain cell types by enhancing either transcription (through nuclear factor-kB and cAMP response element binding protein ) (Hsieh et al, 2007;Park et al, 2007) or stability of COX-2 mRNA (Doller et al, 2007), we became interested in exploring whether PKCs would have similar effects on COX-2 expression in malignant glioma cells. Earlier we found that EGFR signaling induces COX-2 expression in glioma cells in a process requiring p38-MAPK and the activation of the Sp1 transcription factor (Xu and Shu, 2007).…”