PMID- 12110006
OWN - NLM
STAT- MEDLINE
DCOM- 20030113
LR  - 20181130
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 62
IP  - 2
DP  - 2002 Aug
TI  - Effects of different PPARgamma-agonists on MCP-1 expression and monocyte 
      recruitment in experimental glomerulonephritis.
PG  - 455-64
AB  - BACKGROUND: Activators of peroxisome proliferator activated receptor gamma 
      (PPARgamma) have been shown to modulate chemokine expression in isolated 
      monocytes/macrophages (M/M) and to exert anti-inflammatory effects in some models 
      of experimental inflammatory diseases. We evaluated the effects of different 
      forms of PPARgamma activators in a model of experimental glomerulonephritis (GN) 
      in rats. METHODS: GN was induced in rats by application of an anti-thymocyte 
      antibody (ATS). Nephritic rats were treated with two synthetic PPARgamma ligands 
      of the thiazolidinedione (TZD) group, troglitazone (200 mg/kg/day) and 
      ciglitazone (100 mg/kg/day), and with a natural ligand 15d-PGJ2 (1.5 mg/day). 
      Twenty-four hours after induction of the GN, the glomerular mRNA expression of 
      the chemokine monocyte chemoattractant protein-1 (MCP-1) and the cognate 
      chemokine receptor CCR-2 were examined by Northern blotting and RT-PCR. The 
      glomerular M/M infiltration was determined by immunohistology. The activation of 
      the transcription factors PPARgamma, nuclear factor-kappaB (NF-kappaB) and 
      activator protein-1 (AP-1) in glomeruli was analyzed by electrophoretic mobility 
      shift assay. RESULTS: Induction of GN up-regulated glomerular nuclear protein 
      binding of NF-kappaB and AP-1. Treatment of nephritic rats with troglitazone and 
      ciglitazone augmented nuclear PPARgamma and AP-1 DNA binding but did not affect 
      NF-kappaB binding. TZD enhanced glomerular MCP-1 expression and increased 
      glomerular M/M recruitment. In contrast, 15d-PGJ2 attenuated NF-kappaB activation 
      and did not affect AP-1 activity or MCP-1 expression. CONCLUSION: Our data show 
      that PPARgamma activators of the TZD group, but not 15d-PGJ2, enhance MCP-1 
      expression and M/M infiltration in the induction phase of experimental GN. The 
      results demonstrate that TZD and 15d-PGJ2 may exert different effects in the 
      immune response in experimental GN. Our study underscores the need to critically 
      evaluate whether PPARgamma ligands will have beneficial or possibly deleterious 
      effects in GN.
FAU - Panzer, Ulf
AU  - Panzer U
AD  - Zentrum fur Innere Medizin, Medizinische Klinik IV, University of Hamburg, 
      Hamburg, Germany.
FAU - Schneider, Andre
AU  - Schneider A
FAU - Guan, Youfei
AU  - Guan Y
FAU - Reinking, Rudiger
AU  - Reinking R
FAU - Zahner, Gunther
AU  - Zahner G
FAU - Harendza, Sigrid
AU  - Harendza S
FAU - Wolf, Gunter
AU  - Wolf G
FAU - Thaiss, Friedrich
AU  - Thaiss F
FAU - Stahl, Rolf A K
AU  - Stahl RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Ccr2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromans)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Animals
MH  - Cell Movement/immunology
MH  - Chemokine CCL2/*genetics
MH  - Chromans/pharmacology
MH  - Gene Expression/immunology
MH  - Glomerulonephritis/*drug therapy/*immunology
MH  - Hypoglycemic Agents/pharmacology
MH  - Macrophages/cytology
MH  - Male
MH  - Monocytes/*cytology
MH  - NF-kappa B/metabolism
MH  - Nuclear Proteins/metabolism
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics
MH  - Receptors, Cytoplasmic and Nuclear/*agonists/metabolism
MH  - Thiazoles/pharmacology
MH  - *Thiazolidinediones
MH  - Transcription Factor AP-1/metabolism
MH  - Transcription Factors/*agonists/metabolism
MH  - Troglitazone
EDAT- 2002/07/12 10:00
MHDA- 2003/01/14 04:00
CRDT- 2002/07/12 10:00
PHST- 2002/07/12 10:00 [pubmed]
PHST- 2003/01/14 04:00 [medline]
PHST- 2002/07/12 10:00 [entrez]
AID - S0085-2538(15)48572-2 [pii]
AID - 10.1046/j.1523-1755.2002.00476.x [doi]
PST - ppublish
SO  - Kidney Int. 2002 Aug;62(2):455-64. doi: 10.1046/j.1523-1755.2002.00476.x.