PMID- 12734374
OWN - NLM
STAT- MEDLINE
DCOM- 20030826
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 170
IP  - 10
DP  - 2003 May 15
TI  - C-C chemokine ligand 2/monocyte chemoattractant protein-1 directly inhibits NKT 
      cell IL-4 production and is hepatoprotective in T cell-mediated hepatitis in the 
      mouse.
PG  - 5252-9
AB  - T cell-mediated liver diseases are associated with elevated serum levels of C-C 
      chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1). However, 
      the extent to which the actions of CCL2/MCP-1 contribute to the pathogenesis of T 
      cell-mediated hepatitis remains incompletely understood. Con A-induced hepatitis 
      is a liver-specific inflammation mediated by activated T cells and is driven by 
      an up-regulation of the hepatic expression of TNF-alpha, IFN-gamma, and IL-4. The 
      present study examined the role of CCL2/MCP-1 in the pathogenesis of T 
      cell-mediated hepatitis induced by Con A administration in the mouse. We 
      demonstrate a novel hepatoprotective role for CCL2/MCP-1 during Con A-induced 
      hepatitis, because CCL2/MCP-1 neutralization strikingly enhanced hepatic injury, 
      both biochemically and histologically, after Con A administration. Furthermore, 
      CCL2/MCP-1 neutralization was associated with a significant reduction in the 
      hepatic levels of TNF-alpha and IFN-gamma, but with a significant increase in 
      hepatic IL-4 levels. Moreover, IL-4 production and CCR2 expression by Con 
      A-stimulated CD3(+)NK1.1(+) T cells was significantly reduced by rMCP-1 treatment 
      in vitro. In summary, we propose that CCL2/MCP-1 fulfills a novel 
      anti-inflammatory role in T cell-mediated hepatitis by inhibiting CD3(+)NK1.1(+) 
      T cell-derived IL-4 production through direct stimulation of its specific 
      receptor CCR2. These findings may have direct clinical relevance to T 
      cell-mediated hepatitis.
FAU - Ajuebor, Maureen N
AU  - Ajuebor MN
AD  - Liver Unit, Gastrointestinal Research Group, Faculty of Medicine, University of 
      Calgary, Calgary, Alberta, Canada.
FAU - Hogaboam, Cory M
AU  - Hogaboam CM
FAU - Le, Tai
AU  - Le T
FAU - Swain, Mark G
AU  - Swain MG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Immune Sera)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 11028-71-0 (Concanavalin A)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - Cell Movement/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/biosynthesis/immunology/*physiology
MH  - Concanavalin A/toxicity
MH  - Cytokines/antagonists & inhibitors/biosynthesis
MH  - Down-Regulation/immunology
MH  - Hepatitis, Animal/chemically induced/*immunology/pathology/*prevention & control
MH  - Immune Sera/administration & dosage
MH  - Inflammation Mediators/antagonists & inhibitors/immunology/metabolism/*physiology
MH  - Injections, Intraperitoneal
MH  - Injections, Intravenous
MH  - Interleukin-4/*antagonists & inhibitors/biosynthesis
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - Lymphocytes/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/antagonists & inhibitors/biosynthesis
MH  - T-Lymphocyte Subsets/*immunology/*metabolism/pathology
MH  - Up-Regulation/immunology
EDAT- 2003/05/08 05:00
MHDA- 2003/08/27 05:00
CRDT- 2003/05/08 05:00
PHST- 2003/05/08 05:00 [pubmed]
PHST- 2003/08/27 05:00 [medline]
PHST- 2003/05/08 05:00 [entrez]
AID - 10.4049/jimmunol.170.10.5252 [doi]
PST - ppublish
SO  - J Immunol. 2003 May 15;170(10):5252-9. doi: 10.4049/jimmunol.170.10.5252.