Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis

Citation
A. Schneider et al., Cyclooxygenase metabolites mediate glomerular monocyte chemoattractant protein-1 formation and monocyte recruitment in experimental glomerulonephritis, KIDNEY INT, 55(2), 1999, pp. 430-441
Citations number
39
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
KIDNEY INTERNATIONAL
ISSN journal
00852538 → ACNP
Volume
55
Issue
2
Year of publication
1999
Pages
430 - 441
Database
ISI
SICI code
0085-2538(199902)55:2<430:CMMGMC>2.0.ZU;2-#
Abstract
Background. Monocyte chemoattractant protein-1 (MCP-1) has been shown to pl ay a significant role in the recruitment of monocytes/macrophages in experi mental glomerulonephritis. Whereas a number of inflammatory mediators have been characterized that are involved in the expression of MCP-1 in renal di sease, 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 an tibody model and an anti-glomerular basement membrane model of glomerulonep hritis. Rats were treated with the COX-1/COX-2 inhibitor indomethacin and t he 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, e nhanced glomerular MCP-1 and RANTES mRNA levels. Indomethacin enhanced glom erular monocyte chemoattractant activity an the infiltration of monocytes/m acrophages at 24 hours and 5 days. Conclusions. Our studies demontrate that COX products may serve as endogeno us repressors of MCP-I formation in experimental glomerulonephritis. The da ta suggest that COX-1 and COX-2 products mediate these effects differently because the selective COX-2 inhibitors had less influence on chemokine expr ession.