PMID- 9233637
OWN - NLM
STAT- MEDLINE
DCOM- 19970814
LR  - 20100825
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 159
IP  - 3
DP  - 1997 Aug 1
TI  - Identification of an inhibitor targeting macrophage production of monocyte 
      chemoattractant protein-1 as TGF-beta 1.
PG  - 1404-11
AB  - Monocyte chemoattractant protein-1 (MCP-1) is expressed in a diverse range of 
      cells in response to various pathologic stimuli, whereas little is known about 
      endogenous inhibitors of MCP-1 expression. I sought negative regulators of MCP-1 
      in culture medium conditioned by several cell lines and found that glomerular 
      mesangial cells exclusively secrete a factor that inhibits expression of MCP-1 by 
      activated macrophages. Treatment of J774.2 macrophages with conditioned medium 
      from mesangial cells blunted the induction of MCP-1 by LPS. Even after the 
      induction, subsequent treatment of macrophages with the conditioned medium 
      down-regulated the MCP-1 expression. Medium conditioned by normal rat glomeruli 
      contained a similar inhibitory activity that was enhanced in regenerating 
      glomeruli, where mesangial cells are activated. The activity of the conditioned 
      medium was not diminished, but enhanced by heat treatment, which was consistent 
      with the unique property of TGF-beta family of molecules. Indeed, the mesangial 
      cell-derived medium contained active TGF-beta 1. An anti-TGF-beta 1 neutralizing 
      Ab abolished the inhibitory effect exerted by the mesangial cell medium, and 
      externally added TGF-beta 1 suppressed the MCP-1 expression by macrophages at 
      both mRNA and protein levels. The inhibitory effect of TGF-beta 1 on MCP-1 was 
      observed in other macrophage cell lines, RAW264.7 and NR8383, and peritoneal 
      macrophages, but not in fibroblastic cell line NRK49F. Treatment of J774.2 
      macrophages with TGF-beta 1 inhibited LPS induction of c-jun that was found to be 
      crucial for the MCP-1 expression. These data demonstrate that TGF-beta 1 
      functions as an inhibitor of MCP-1 expression in macrophages possibly via 
      down-regulation of c-Jun/activator protein-1.
FAU - Kitamura, M
AU  - Kitamura M
AD  - Department of Medicine, University College London Medical School, United Kingdom. 
      m.kitamura@medicine.ucl.ac.uk
LA  - eng
GR  - Wellcome Trust/United Kingdom
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 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/*antagonists & inhibitors/*biosynthesis
MH  - Culture Media, Conditioned/chemistry/pharmacology
MH  - Dose-Response Relationship, Immunologic
MH  - Glomerular Mesangium/physiology
MH  - Glomerulonephritis/immunology/metabolism
MH  - Immunosuppressive Agents/chemistry/pharmacology
MH  - Kidney Glomerulus/immunology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophage Activation/drug effects
MH  - Macrophages/*drug effects/*metabolism
MH  - Male
MH  - Proto-Oncogene Proteins c-jun/drug effects
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Sprague-Dawley
MH  - Transcription Factor AP-1/drug effects
MH  - Transforming Growth Factor beta/chemistry/*pharmacology
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1997 Aug 1;159(3):1404-11.