PMID- 18160487
OWN - NLM
STAT- MEDLINE
DCOM- 20080501
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 294
IP  - 3
DP  - 2008 Mar
TI  - Role of PKC-delta on substance P-induced chemokine synthesis in pancreatic acinar 
      cells.
PG  - C683-92
AB  - 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-kappaB. However, the signaling mechanisms by which the SP-NK1R interaction 
      induces NF-kappaB 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-kappaB 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-kappaB, 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.
FAU - Ramnath, Raina Devi
AU  - Ramnath RD
AD  - Dept. of Pharmacology, National Univ. of Singapore, Yong Loo Lin School of 
      Medicine, Centre for life Sciences, 28 Medical Drive, Singapore 117456.
FAU - Sun, Jia
AU  - Sun J
FAU - Adhikari, Sharmila
AU  - Adhikari S
FAU - Zhi, Liang
AU  - Zhi L
FAU - Bhatia, Madhav
AU  - Bhatia M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071226
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Acetophenones)
RN  - 0 (Benzopyrans)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccl3 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cxcl2 protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Neurokinin-1 Receptor Antagonists)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Neurokinin-1)
RN  - 0 (Transcription Factor AP-1)
RN  - 33507-63-0 (Substance P)
RN  - E29LP3ZMUH (rottlerin)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - W22ILA2I52 (CP 96345)
SB  - IM
MH  - Acetophenones/pharmacology
MH  - Animals
MH  - Benzopyrans/pharmacology
MH  - Biphenyl Compounds/pharmacology
MH  - Chemokine CCL2/biosynthesis
MH  - Chemokine CCL3/biosynthesis
MH  - Chemokine CXCL2/biosynthesis
MH  - Chemokines/*biosynthesis/genetics
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - MAP Kinase Kinase Kinase 1/metabolism
MH  - MAP Kinase Kinase Kinases/metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Neurokinin-1 Receptor Antagonists
MH  - Pancreas, Exocrine/cytology/drug effects/enzymology/*metabolism
MH  - Phosphorylation
MH  - Protein Kinase C-delta/antagonists & inhibitors/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Receptors, Neurokinin-1/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Substance P/*metabolism
MH  - Time Factors
MH  - Transcription Factor AP-1/metabolism
EDAT- 2007/12/28 09:00
MHDA- 2008/05/02 09:00
CRDT- 2007/12/28 09:00
PHST- 2007/12/28 09:00 [pubmed]
PHST- 2008/05/02 09:00 [medline]
PHST- 2007/12/28 09:00 [entrez]
AID - 00360.2007 [pii]
AID - 10.1152/ajpcell.00360.2007 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2008 Mar;294(3):C683-92. doi: 
      10.1152/ajpcell.00360.2007. Epub 2007 Dec 26.