Hoecherl, Klaus and Dreher, Franziska and Vitzthum, Helga and Koehler, Jens and Kurtz, Armin (2002) Cyclosporine A suppresses cyclooxygenase-2 expression in the rat kidney. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 13 (10). pp. 2427-2436. ISSN 1046-6673
Full text not available from this repository. (Request a copy)Abstract
On the basis of recent evidence that the cyclooxygenase-2 (COX-2) gene promoter contains functional binding sites for the nuclear factor of activated T cells (NFAT) and that COX-2 is expressed in a regulated fashion in the kidney, this study aimed to assess the effect of immunosuppressants on COX-2 expression in the kidney. Therefore, Wistar-Kyoto rats were treated with cyclosporine A (CsA; 15 mg/kg per day) or tacrolimus (5 mg/kg per day) for 7 d each. Both drugs markedly lowered COX-2 expression while COX-1 expression remained unaltered. Furthermore, CsA blunted the increase of renocortical COX-2 expression in response to low salt intake or a combination of low-salt diet with the ACE inhibitor ramipril (10 mg/kg per day), which strongly stimulates renocortical COX-2 expression. At the same time, calcineurin inhibitors moderately enhanced basal as well as stimulated renin secretion and renin gene expression. These findings suggest that inhibition of calcineurin could be a crucial determinant for the regulated expression of COX-2 in the kidney. Inhibition of COX-2 expression may therefore at least in part account for the well-known adverse effects of immunosuppressants in the kidney. Moreover, our data suggest that the stimulation of the renin system by low salt and by ACE inhibitors is not essentially mediated by COX-2 activity.
Item Type: | Article |
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Uncontrolled Keywords: | ACTIVATED T-CELLS; RENIN-ANGIOTENSIN SYSTEM; NUCLEAR FACTOR; MACULA DENSA; INDUCED NEPHROTOXICITY; TRANSCRIPTION FACTOR; MOLECULAR-BIOLOGY; STIMULATED RENIN; RESPONSE ELEMENT; MATRIX PROTEINS; |
Subjects: | 500 Science > 570 Life sciences 600 Technology > 615 Pharmacy |
Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
Depositing User: | Dr. Gernot Deinzer |
Date Deposited: | 05 Oct 2021 06:04 |
Last Modified: | 05 Oct 2021 06:04 |
URI: | https://pred.uni-regensburg.de/id/eprint/39841 |
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