The role of tumor necrosis factor-α converting enzyme in renal transplant rejection.
BACKGROUND
Tumor necrosis factor receptors (TNFR) are differentially regulated in human rejecting renal transplants. The TNF-α converting enzyme (TACE) regulates the membrane shedding of both receptors and TNF itself. We analyzed the expression and regulation of TACE in human rejecting renal transplants.


METHODS
Samples from normal renal tissue or renal transplant undergoing severe acute rejection were immunostained for TACE using antibodies from different species. Human kidney epithelial cells were cultured and TACE plasmid was transfected to upregulate TACE expression. Cells were fractionated and immunoblotted for TACE, and ELISA was performed to test soluble TNFR2.


RESULTS
We showed that TACE was upregulated mainly in tubular epithelial cells in acute rejecting kidney, where it colocalized with TNFR2. Epithelial cells with increased levels of TACE shed more soluble TNFR2 into culture media and even more after TACE activation by phorbol-12-myristate-13-acetate stimulation. The shedding could be completely blocked by the TACE inhibitor TNF-α protease inhibitor.


CONCLUSIONS
Upregulation of TACE in epithelial cells in acute rejecting kidney could lead to more TNFR2 shedding and, hence, antagonize the proinflammatory effect of local TNF.
Wang
Jun
J
Department of Nephrology, First Hospital of China Medical University, Shenyang, PR China. jw270uk@hotmail.co.uk
Li
Zilong
Z
Al-Lamki
Rafia
R
Wang
Juan
J
Zuo
Nan
N
Bradley
John R
JR
Wang
Lining
L
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D002478:Cells, Cultured / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006084:Graft Rejection / Q000201:enzymology*; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015854:Up-Regulation
D018124:Receptors, Tumor Necrosis Factor; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human