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

Background. Chronic interstitial scarring contributes to the progression of renal failure in glomerular disease but its cause is unknown. The developm ent of proteinuria could stimulate tubular cells to release cytokines, chem oattractants and matrix proteins into the interstitium, thus contributing t o interstitial disease. Methods. Polarized human tubular epithelial cells were grown on permeable s upports and exposed to serum proteins on their apical surface. The release of tumour necrosis factor alpha(TNF alpha), platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1 (MCP-1) by the cells was meas ured using immunoassays. Results. Under control conditions there was polarized release of PDGF-AB wi th predominant basolateral secretion (basolateral to apical ratio 4.7 +/- 1 .6). MCP-1 release was less polarized (ratio 1.7+/-0.5). TNF alpha was not detected. Exposure of the cells to normal human serum proteins on their api cal 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 h uman tubular epithelial cells was reproduced by a fraction of molecular wei ght 40-100 kDa. The predominant proteins in this fraction were albumin and transferrin but these purified proteins alone did not alter secretion of PD GF-AB or MCP-1. Conclusion, This data demonstrates that human tubular cells exposed to prot eins, which would be filtered in glomerular disease, produce inflammatory m ediators with the potential to stimulate inflammation and scarring in the i nterstitium of the kidney.