The significant role of RANTES and CCR5 in progressive tubulointerstitial lesions in lupus nephropathy.
Glomerulonephritis is an important cause of end-stage renal failure, yet the pathogenetic mechanisms of most forms of glomerulonephritis are not clear. Renal fibrosis is the final common pathway for many kidney lesions that lead to chronic progressive organ failure. Recent study suggests that chemokines and chemokine receptors are involved in the resolution or progression of renal diseases. In view of the above we detected using immunohistochemistry the expression of RANTES, CCR5+ cells,TGF-beta1, alpha-SMA in renal biopsy specimens in 17 patients with IVG A/C class of lupus nephritis and in 10 normal kidneys. The correlative study was undertaken to evaluate the possible relationships between the immunoexpression of RANTES, the number of CCR5+ cells, the immunoexpression of TGF-beta1, alpha-SMA, the value of interstitial cortical volume and the serum creatinine level in patients with lupus nephropathy. Statistical analysis revealed significant increase in tubulointerstitial RANTES immunoexpression in lupus nephritis as compared to normal controls. In our study CCR5+ cells were detected in the interstitium in tissue samples in patient with lupus nephritis, meanwhile no CCR5+ cells were documented in normal controls. We found a strong positive correlation between tubulointerstitial immunoexpression of RANTES and the number of interstitial CCR5+ cells as well as between immunoexpression of RANTES and the immunoexpression of TGF-beta1, alpha-SMA, renal cortical volume and serum creatinine in patients with lupus nephritis. Moreover, the number of interstitial CCR5+ cells was positively correlated with tubulointerstitial alpha-SMA immunoexpression and renal cortical volume. In summary, the results suggest that in lupus nephritis RANTES may participate in interstitial lesions via CCR5+ cells.
Stasikowska
Olga
O
Department of Nephropathology, Medical University of Lódź.
Danilewicz
Marian
M
Wagrowska-Danilewicz
Małgorzata
M
D000199:Actins / Q000096:biosynthesis; D000328:Adult; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D000199:Actins; D018946:Chemokine CCL5; D019713:Receptors, CCR5; D053773:Transforming Growth Factor beta1; D003404:Creatinine