Abstract
Fas ligand (FasL) is a cell membrane cytokine that can promote apoptosis through activation of Fas receptors. Fas receptor activation induces glomerular cell apoptosis in vivo and participates in tubular cell death during acute renal failure. However, there is little information on the expression of FasL in the kidney. This study reports that FasL mRNA and protein are present in normal mouse and rat kidney. In situ hybridization and immunohistochemistry showed that proximal tubular epithelium is the main site of FasL expression in the normal kidney. In addition, increased total kidney FasL mRNA and de novo FasL protein expression by glomerular cells were observed in two different models of glomerular injury : rat immune-complex proliferative glumerulonephritis and murine lupus nephritis. Both full-length and soluble FasL were increased in the kidneys of the mice with nephritis. Cultured murine proximal tubular epithelial MCT cells and primary cultures of murine tubular epithelial cells expressed FasL mRNA and protein. Tubular epithelium-derived FasL induced apoptosis in Fassensitive lymphoid cell lines but not in Fas-resistant lymphoid cell lines. By contrast, MCT cells grown in the presence of the survival factors of serum were resistant to FasL, and only became partially sensitive to apoptosis induced by high concentrations (100 ng/ml) of FasL upon serum deprivation. However, MCT cells stimulated with inflammatory mediators (tumor necrosis factor-alpha, interferon-gamma, and lipopolysaccharide) increased cell surface Fas expression and were sensitized to apoptosis induced by FasL (FasL 55 +/- 5% versus control 8.3 +/- 4.1% apoptotic cells at 24 h, P < 0.05). Cytokine-primed primary cultures of tubular epithelial cells also acquired sensitivity to FasL-induced apoptosis. These results suggest that FasL expression by intrinsic renal cells may play a role in cell homeostasis in the normal kidney and during renal injury.
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Schedule a callMore From: Journal of the American Society of Nephrology : JASN
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