Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins.
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 alpha(TNFalpha), 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). TNFalpha 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.


CONCLUSIONS
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.
Burton
C J
CJ
Department of Nephrology, Leicester General Hospital, Leicester, UK.
Combe
C
C
Walls
J
J
Harris
K P
KP
D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012709:Serum Albumin / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001798:Blood Proteins; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D012709:Serum Albumin; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha; C095477:platelet-derived growth factor AB