Nephrol Dial Transplant (1999) 14: 2628-2633
© 1999 European Renal Association-European Dialysis and Transplant Association
Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins
Department of Nephrology, Leicester General Hospital, Leicester, UK
Correspondence and offprint requests to: Dr Chris Burton, Senior Registrar in Renal Medicine, The Richard Bright Renal Unit, Westbury-on-Trym, Bristol BS10 5NB, UK.
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 
(TNF), 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). TNF 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
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E.J. Reinders, W. E. Fibbe, and T. J. Rabelink Multipotent mesenchymal stromal cell therapy in renal disease and kidney transplantation Nephrol. Dial. Transplant., October 26, 2009; (2009) gfp552v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hertig, D. Anglicheau, J. Verine, N. Pallet, M. Touzot, P.-Y. Ancel, L. Mesnard, N. Brousse, E. Baugey, D. Glotz, et al. Early Epithelial Phenotypic Changes Predict Graft Fibrosis J. Am. Soc. Nephrol., August 1, 2008; 19(8): 1584 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Floege, F. Eitner, and C. E. Alpers A New Look at Platelet-Derived Growth Factor in Renal Disease J. Am. Soc. Nephrol., January 1, 2008; 19(1): 12 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Waldman, R. J. Crew, A. Valeri, J. Busch, B. Stokes, G. Markowitz, V. D'Agati, and G. Appel Adult Minimal-Change Disease: Clinical Characteristics, Treatment, and Outcomes Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 445 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abbate, C. Zoja, and G. Remuzzi How Does Proteinuria Cause Progressive Renal Damage? J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2974 - 2984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Prakash, M. Sandovici, V. Saluja, M. Lacombe, R. Q. J. Schaapveld, M. H. de Borst, H. van Goor, R. H. Henning, J. H. Proost, F. Moolenaar, et al. Intracellular Delivery of the p38 Mitogen-Activated Protein Kinase Inhibitor SB202190 [4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in Renal Tubular Cells: A Novel Strategy to Treat Renal Fibrosis J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 8 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Brunskill Albumin Signals the Coming of Age of Proteinuric Nephropathy J. Am. Soc. Nephrol., February 1, 2004; 15(2): 504 - 505. [Full Text] [PDF]
|
|
|
|
|
|
D. Zheng, M. Wolfe, B. D. Cowley Jr., D. P. Wallace, T. Yamaguchi, and J. J. Grantham Urinary Excretion of Monocyte Chemoattractant Protein-1 in Autosomal Dominant Polycystic Kidney Disease J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2588 - 2595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nishino, C. D. Pusey, and J. Domin Elevated Akt Phosphorylation as an Indicator of Renal Tubular Epithelial Cell Stress J. Biol. Chem., September 6, 2002; 277(37): 33943 - 33949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Osterby, H.-J. Bangstad, and S. Rudberg Follow-up study of glomerular dimensions and cortical interstitium in microalbuminuric type 1 diabetic patients with or without antihypertensive treatment Nephrol. Dial. Transplant., October 1, 2000; 15(10): 1609 - 1616. [Abstract] [Full Text] [PDF]
|
|