PMID- 10534503
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20220321
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 14
IP  - 11
DP  - 1999 Nov
TI  - Secretion of chemokines and cytokines by human tubular epithelial cells in 
      response to proteins.
PG  - 2628-33
AB  - 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. 
      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.
FAU - Burton, C J
AU  - Burton CJ
AD  - Department of Nephrology, Leicester General Hospital, Leicester, UK.
FAU - Combe, C
AU  - Combe C
FAU - Walls, J
AU  - Walls J
FAU - Harris, K P
AU  - Harris KP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Blood Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Serum Albumin)
RN  - 0 (Transferrin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (platelet-derived growth factor AB)
SB  - IM
MH  - Blood Proteins/chemistry/*pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Chemokines/*metabolism
MH  - Cytokines/*metabolism
MH  - Epithelial Cells/drug effects/metabolism
MH  - Humans
MH  - Kidney Tubules/cytology/drug effects/*metabolism
MH  - Molecular Weight
MH  - Platelet-Derived Growth Factor/metabolism
MH  - Serum Albumin/pharmacology
MH  - Transferrin/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1093/ndt/14.11.2628 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 1999 Nov;14(11):2628-33. doi: 10.1093/ndt/14.11.2628.