PMID- 16873895
OWN - NLM
STAT- MEDLINE
DCOM- 20061226
LR  - 20061108
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 291
IP  - 6
DP  - 2006 Dec
TI  - Substance P treatment stimulates chemokine synthesis in pancreatic acinar cells 
      via the activation of NF-kappaB.
PG  - G1113-9
AB  - Acinar cell injury early in acute pancreatitis leads to a local inflammatory 
      reaction and to the subsequent systemic inflammatory response, which may result 
      in multiple organ dysfunction and death. Inflammatory mediators, including 
      chemokines and substance P (SP), are known to play a crucial role in the 
      pathogenesis of acute pancreatitis. It has been shown that pancreatic acinar 
      cells produce the chemokine monocyte chemoattractant protein-1 (MCP-1) in 
      response to caerulein hyperstimulation, demonstrating that acinar-derived MCP-1 
      is an early mediator of inflammation in acute pancreatitis. Similarly, SP levels 
      in the pancreas and pancreatic acinar cell expression of neurokinin-1 receptor, 
      the primary receptor for SP, are both increased during secretagogue-induced 
      experimental pancreatitis. This study aims to examine the functional consequences 
      of exposing mouse pancreatic acinar cells to SP and to determine whether it leads 
      to proinflammatory signaling, such as production of chemokines. Exposure of mouse 
      pancreatic acini to SP significantly increased synthesis of MCP-1, macrophage 
      inflammatory protein-1alpha (MIP-1alpha), as well as MIP-2. Furthermore, SP also 
      increased NF-kappaB activation. The stimulatory effect of SP was specific to 
      chemokine synthesis through the NF-kappaB pathway, since the increase in 
      chemokine production was completely attenuated when pancreatic acini were 
      pretreated with the selective NF-kappaB inhibitor NF-kappaB essential 
      modulator-binding domain peptide. This study shows that SP-induced chemokine 
      synthesis in mouse pancreatic acinar cells is NF-kappaB dependent.
FAU - Ramnath, Raina Devi
AU  - Ramnath RD
AD  - Department of Pharmacology, National University of Singapore, Singapore.
FAU - Bhatia, Madhav
AU  - Bhatia M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060727
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Chemokines)
RN  - 0 (NF-kappa B)
RN  - 33507-63-0 (Substance P)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokines/*biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Pancreas/*cytology/drug effects/*metabolism
MH  - Substance P/*administration & dosage
EDAT- 2006/07/29 09:00
MHDA- 2006/12/27 09:00
CRDT- 2006/07/29 09:00
PHST- 2006/07/29 09:00 [pubmed]
PHST- 2006/12/27 09:00 [medline]
PHST- 2006/07/29 09:00 [entrez]
AID - 00177.2006 [pii]
AID - 10.1152/ajpgi.00177.2006 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2006 Dec;291(6):G1113-9. doi: 
      10.1152/ajpgi.00177.2006. Epub 2006 Jul 27.