PMID- 12388376
OWN - NLM
STAT- MEDLINE
DCOM- 20030314
LR  - 20220227
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 284
IP  - 2
DP  - 2003 Feb
TI  - Alveolar epithelial cell inhibition of fibroblast proliferation is regulated by 
      MCP-1/CCR2 and mediated by PGE2.
PG  - L342-9
AB  - CC chemokine receptor 2 (CCR2) -/- mice are protected from experimental pulmonary 
      fibrosis, a disease increasingly recognized as being mediated by dysfunctional 
      interactions between epithelial cells and fibroblasts. We have sought to 
      investigate the interactions between alveolar epithelial cells (AECs) and 
      fibroblasts in these fibrosis-resistant (CCR2 -/-) and fibrosis-sensitive (CCR2 
      +/+) mice. AECs from CCR2 -/- mice suppress fibroblast proliferation more than 
      AECs from CCR2 +/+ mice (77 vs. 43%). Exogenous administration of the CCR2 ligand 
      monocyte chemoattractant protein-1 (MCP-1) to the fibroblast-AEC cocultures 
      reverses the suppression mediated by CCR2 +/+ AECs but has no effect with CCR2 
      -/- AECs. MCP-1 regulates AEC function but not fibroblast function. AEC 
      inhibition of fibroblast proliferation was mediated by a soluble, 
      aspirin-sensitive factor. Accordingly, AECs from CCR2 -/- mice produce greater 
      quantities of PGE(2) than do AECs from CCR2 +/+ mice, and MCP-1 inhibits 
      AEC-derived PGE(2) synthesis. Diminished PGE(2) production by AECs results in 
      enhanced fibroproliferation. Thus an important profibrotic mechanism of 
      MCP-1/CCR2 interactions is to limit PGE(2) production in AECs after injury, thus 
      promoting fibrogenesis.
FAU - Moore, Bethany B
AU  - Moore BB
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, University of Michigan Medical School, 6301 MSRB III, 1150 W. Medical 
      Center Drive, Ann Arbor, MI 48109, USA. Bmoore@umich.edu
FAU - Peters-Golden, Marc
AU  - Peters-Golden M
FAU - Christensen, Paul J
AU  - Christensen PJ
FAU - Lama, Vibha
AU  - Lama V
FAU - Kuziel, William A
AU  - Kuziel WA
FAU - Paine, Robert 3rd
AU  - Paine R 3rd
FAU - Toews, Galen B
AU  - Toews GB
LA  - eng
GR  - P50 HL 56402/HL/NHLBI NIH HHS/United States
GR  - P50 HL 60289/HL/NHLBI NIH HHS/United States
GR  - R01 HL 51082/HL/NHLBI NIH HHS/United States
GR  - R29 CA 79046/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20021004
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Prostaglandins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Cell Division/drug effects/physiology
MH  - Chemokine CCL2/pharmacology/*physiology
MH  - Dinoprostone/antagonists & inhibitors/*physiology
MH  - Epithelial Cells/drug effects/physiology
MH  - Fibroblasts/*cytology
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout/genetics
MH  - Prostaglandins/biosynthesis
MH  - Pulmonary Alveoli/drug effects/*physiology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/*physiology
EDAT- 2002/10/22 04:00
MHDA- 2003/03/15 04:00
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2003/03/15 04:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
AID - 00168.2002 [pii]
AID - 10.1152/ajplung.00168.2002 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L342-9. doi: 
      10.1152/ajplung.00168.2002. Epub 2002 Oct 4.