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
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.