Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis.
BACKGROUND
Monocyte chemoattractant protein-1 (MCP-1) has been shown to play a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal disease, little is known about repressors of chemokine formation in vivo. We hypothesized that cyclooxygenase (COX) products influence the formation of MCP-1 and affect inflammatory cell recruitment in glomerulonephritis.


METHODS
The effect of COX inhibitors was evaluated in the antithymocyte antibody model and an anti-glomerular basement membrane model of glomerulonephritis. Rats were treated with the COX-1/COX-2 inhibitor indomethacin and the selective COX-2 inhibitors meloxicam and SC 58125. Animals were studied at 1 hour, 24 hours, and 5 days after induction of the disease.


RESULTS
Indomethacin, to a lesser degree the selective COX-2 inhibitors, enhanced glomerular MCP-1 and RANTES mRNA levels. Indomethacin enhanced glomerular monocyte chemoattractant activity an the infiltration of monocytes/macrophages at 24 hours and 5 days.


CONCLUSIONS
Our studies demonstrate that COX products may serve as endogenous repressors of MCP-1 formation in experimental glomerulonephritis. The data suggest that COX-1 and COX-2 products mediate these effects differently because the selective COX-2 inhibitors had less influence on chemokine expression.
Schneider
A
A
Department of Medicine, University of Hamburg, Germany.
Harendza
S
S
Zahner
G
G
Jocks
T
T
Wenzel
U
U
Wolf
G
G
Thaiss
F
F
Helmchen
U
U
Stahl
R A
RA
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009000:Monocytes / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar