Journal Article

Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins

Christopher J. Burton, Christian Combe, John Walls and Kevin P. G. Harris

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 14, issue 11, pages 2628-2633
Published in print November 1999 | ISSN: 0931-0509
Published online November 1999 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/14.11.2628
Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins

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Background. Chronic interstitial scarring contributes to the progression of renal failure in glomerular disease but its cause is unknown. The development of proteinuria could stimulate tubular cells to release cytokines, chemoattractants and matrix proteins into the interstitium, thus contributing to interstitial disease.

Methods. Polarized human tubular epithelial cells were grown on permeable supports and exposed to serum proteins on their apical surface. The release of tumour necrosis factor α(TNFα), platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1 (MCP-1) by the cells was measured using immunoassays.

Results. Under control conditions there was polarized release of PDGF-AB with predominant basolateral secretion (basolateral to apical ratio 4.7±1.6). MCP-1 release was less polarized (ratio 1.7±0.5). TNFα was not detected. Exposure of the cells to normal human serum proteins on their apical side increased basolateral release of PDGF-AB (1.7±0.4 fold) and MCP-1 (2.4±0.2 fold). Fractionation of the serum showed that this effect on human tubular epithelial cells was reproduced by a fraction of molecular weight 40–100 kDa. The predominant proteins in this fraction were albumin and transferrin but these purified proteins alone did not alter secretion of PDGF-AB or MCP-1.

Conclusion. This data demonstrates that human tubular cells exposed to proteins, which would be filtered in glomerular disease, produce inflammatory mediators with the potential to stimulate inflammation and scarring in the interstitium of the kidney.

Keywords: interstitial scarring; monocyte chemoattractant protein-1; platelet derived growth factor; proteinuria; proximal tubular cell

Journal Article.  3808 words.  Illustrated.

Subjects: Nephrology

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