Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 294, Issue 3, Pages C683-C692Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00360.2007
Keywords
protein kinse C-delta; mitogen-activated protein kinase kinase kinase-1; extracellular signal-regulated kinase; c-Jun NH2-terminal kinase; nuclear factor-kappa B; activator protein-1
Categories
Ask authors/readers for more resources
Interaction of the neuropeptide substance P (SP) with its high-affinity neurokinin-1 receptor (NK1R) plays an important role in the pathophysiology of acute pancreatitis. SP is known to stimulate the production of chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha, and MIP-2 in pancreatic acinar cells via the activation of NF-kappa B. However, the signaling mechanisms by which the SP-NK1R interaction induces NF-kappa B activation and chemokine production remain unclear. To that end, in the present study, we investigated the participation of PKC in SP-induced chemokine production in pancreatic acinar cells. In this study, we showed that SP stimulated an early phosphorylation of PKC isoform PKC-delta followed by increased activation of MAPKKK MEKK1 and MAPK ERK and JNK as well as transcription factor NF-kappa B and activator protein-1 driven chemokine production. Depletion of PKC-delta with its inhibitor rottlerin or the specific PKC-delta translocation inhibitor peptide dose dependently decreased SP-induced PKC-delta, MEKK1, ERK, JNK, NF-kappa B, and AP-1 activation. Moreover, rottlerin as well as PKC-delta translocation inhibitor inhibited SP-induced chemokine production in a concentration-dependent manner. We also demonstrated that PKC-delta activation was attenuated by CP96345, a selective NK1R antagonist, thus showing that PKC-delta activation was indeed mediated by SP in pancreatic acinar cells. These results show that PKC-delta is an important proinflammatory signal transducer for SP-NK1R-induced chemokine production in pancreatic acinar cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available