PMID- 17303665
OWN - NLM
STAT- MEDLINE
DCOM- 20070604
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 148
IP  - 5
DP  - 2007 May
TI  - Induction of monocyte chemoattractant protein-1 expression by angiotensin II in 
      the pancreatic islets and beta-cells.
PG  - 2198-208
AB  - Angiotensin II (AngII), the principal hormone of the renin-angiotensin system, is 
      actively generated in the pancreas and has been suggested as a key mediator of 
      inflammation. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that 
      plays an important role in the recruitment of mononuclear cells into the 
      pancreatic islets. In this study, we investigated the potential molecular basis 
      for the role of AngII in islet inflammation through studying its effect on MCP-1. 
      AngII significantly increased the expression of MCP-1 mRNA and protein in the 
      RINm5F beta-cell line and activated MCP-1 promoter. AngII-MCP-1 mRNA induction 
      was inhibited by an AngII type 1 receptor antagonist but was unchanged by an 
      AngII type 2 receptor antagonist. AngII-MCP-1 induction was inhibited by the 
      tyrosine kinase inhibitor genistein, suggesting a MAPK signaling mechanism. AngII 
      activated the phosphorylation of ERK1/2 but not p38 or c-Jun NH(2)-terminal 
      MAPKs. Inhibition of ERK1/2 activation reduced the AngII-induced MCP-1 synthesis. 
      In nonobese diabetic mice pancreata, the temporal pattern of 
      angiotensin-converting enzyme expression correlated well with progression of 
      insulitis and beta-cell destruction. Immunostaining of pancreatic serial sections 
      show colocalization of angiotensin-converting enzyme with MCP-1 in beta-cells in 
      the islets. In freshly isolated islets from normoglycemic mice, AngII alone and 
      in combination with IL-1beta elicited an inflammatory response by stimulation of 
      MCP-1. Our data suggest a positive autocrine/paracrine action for the local 
      pancreatic AngII-generating system during insulitis and provide the first insight 
      into an AngII-initiated signal transduction pathway that regulates MCP-1 as a 
      possible inflammatory mechanism in the islets.
FAU - Chipitsyna, Galina
AU  - Chipitsyna G
AD  - Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, 
      USA.
FAU - Gong, Qiaoke
AU  - Gong Q
FAU - Gray, Chance F
AU  - Gray CF
FAU - Haroon, Yasir
AU  - Haroon Y
FAU - Kamer, Erdinc
AU  - Kamer E
FAU - Arafat, Hwyda A
AU  - Arafat HA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070215
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Vasoconstrictor Agents)
RN  - 11128-99-7 (Angiotensin II)
RN  - 130663-39-7 (PD 123319)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Angiotensin II/*pharmacology
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/*genetics
MH  - Diabetes Mellitus, Type 1/immunology/*physiopathology
MH  - Gene Expression/drug effects/immunology
MH  - Hyperglycemia/immunology/physiopathology
MH  - Imidazoles/pharmacology
MH  - Insulin-Secreting Cells/drug effects/*physiology
MH  - Insulinoma
MH  - Interleukin-1beta/pharmacology
MH  - Losartan/pharmacology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Pancreatic Neoplasms
MH  - Promoter Regions, Genetic/physiology
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Vasoconstrictor Agents/*pharmacology
EDAT- 2007/02/17 09:00
MHDA- 2007/06/05 09:00
CRDT- 2007/02/17 09:00
PHST- 2007/02/17 09:00 [pubmed]
PHST- 2007/06/05 09:00 [medline]
PHST- 2007/02/17 09:00 [entrez]
AID - en.2006-1358 [pii]
AID - 10.1210/en.2006-1358 [doi]
PST - ppublish
SO  - Endocrinology. 2007 May;148(5):2198-208. doi: 10.1210/en.2006-1358. Epub 2007 Feb 
      15.