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Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment
A Schneider1, S Harendza, G Zahner
1Department of Medicine, University of Hamburg, Germany.
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.