Role of CXCR1 (CKR-1) in inflammation of experimental mesangioproliferative glomerulonephritis
Fatih Ozaltin1, Nesrin Besbas, Alper Bektas Iskit
1Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. fozaltin@hacettepe.edu.tr
Insights
Cyclosporine A (CsA) treatment inhibited the expression of CXCR1, a receptor involved in inflammation, in rats with experimental glomerulonephritis. This suggests CsA may be beneficial by reducing inflammation associated with CXCR1.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Glomerular diseases involve neutrophils and monocytes, which express CXCR1, a receptor for IL-8.
- CXCR1 plays a role in inflammatory processes within the kidneys.
Purpose of the Study:
- To investigate the time-dependent expression of CXCR1 in experimental mesangioproliferative glomerulonephritis.
- To evaluate the effect of single-dose cyclosporine A (CsA) on CXCR1 expression in this model.
Main Methods:
- Experimental mesangioproliferative glomerulonephritis was induced in Wistar rats using anti-thymocyte serum (ATS).
- Rats were divided into control, ATS-induced nephritis, and ATS + CsA treatment groups.
- Kidney tissues were collected at various time points (6 hours, 3, 5, and 7 days) for analysis.
Main Results:
- ATS induced significant proteinuria, glomerular inflammation, mesangial proliferation, and interstitial inflammation compared to controls.
- CsA treatment precluded the development of proteinuria and reduced inflammation and proliferation.
- ATS induced CXCR1 expression in glomeruli and tubulointerstitium, which was inhibited by CsA, particularly within the first 6 hours.
Conclusions:
- CXCR1 expression is upregulated in experimental mesangioproliferative glomerulonephritis.
- CsA treatment effectively inhibits CXCR1 expression and associated inflammation in this model.
- CXCR1 may contribute to the pathogenesis of glomerulonephritis, and CsA's inhibitory effect on CXCR1 suggests a potential therapeutic benefit.
Abstract:
CXCR1 (CKR-1), a receptor of IL-8, is expressed in various cells including neutrophils and monocytes, both of which play a major role in proliferating glomerular diseases. We investigated time-dependent expression of CXCR1 and the effect of single-dose cyclosporine A (CsA) treatment on this expression in experimental mesangioproliferative glomerulonephritis induced by anti-thymocyte serum (ATS). Wistar rats were divided into three groups. Group 1 (control, n = 24) received non-immune serum. Group 2 (nephritis, n = 24) received ATS. Group 3 (nephritis + CsA, n = 24) received ATS and CsA concomitantly. Kidneys from six rats in each group were removed at sixth hour, 3 days, 5 days, and 7 days. ATS induced proteinuria compared to controls (p < 0.001) and CsA precluded the development of proteinuria. Glomerular inflammation and mesangial proliferation were significantly higher in ATS group than control and CsA-treated rats (p < 0.001). ATS injection caused marked interstitial inflammation that was precluded by CsA (p < 0.001). CXCR1 was not expressed in control kidneys. However, ATS induced expression of CXCR1 in both glomeruli and tubulointerstitium. CsA treatment precluded CXCR1 expression in both glomeruli and tubulointerstitium only in the first 6 h. CXCR1 may contribute to inflammation in experimental mesangioproliferative glomerulonephritis. CsA may be beneficial by inhibiting CXCR1 expression and corresponding inflammation.
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