Role of CXCR1 (CKR-1) in Inflammation of Experimental Mesangioproliferative Glomerulonephritis

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.