TL1-A can engage death receptor-3 and activate NF-kappa B in endothelial cells.
BACKGROUND
Death receptors (DRs) play an important role in renal pathology. We have shown that DR3 is inducibly expressed on renal tubular epithelial cells in the setting of inflammatory injuries. In this study we investigate the expression of DR3 in renal endothelial cells and their response to TL1A, the only known ligand of DR3.


METHODS
We did RT-PCR, flow cytometry and subcellular immunoblotting to examine the expression and function of DR3 in cells in vitro. We did organ culture of human and mouse tissue to examine expression and signal of DR3 in vivo.


RESULTS
DR3 is expressed in some interstitial vascular endothelial cells (EC) in human kidney in situ; these EC also respond to its ligand TL1A by activating NF-κB. Very low levels of DR3 can be detected on the cell surface of cultured human umbilical vein (HUV) EC, which do not respond to TL1A. HUVEC transfected to overexpress DR3 become responsive to TL1A, assessed by IκBα degradation and E-selectin induction, indicating that the signaling components needed for DR3 responsiveness are expressed. TL1A induces NF-κB activation in EC in renal and cardiac tissue from wild type but not DR3 knock-out mice.


CONCLUSIONS
TL1A and DR3 activate NF-κB in vascular endothelial cells, and can be an important regulator of renal interstitial vascular injury.
Department of nephrology, First Hospital of China Medical University, Nanjing Street, 110001 Shenyang, P,R, China. jw270uk@hotmail.co.uk.
Jun
J
Wang
Rafia S
RS
Al-Lamki
Xinwang
X
Zhu
Hanzhe
H
Liu
Jordan S
JS
Pober
John R
JR
Bradley
D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009924:Organ Culture Techniques; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000494:pharmacology / Q000502:physiology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D053219:Receptors, Tumor Necrosis Factor, Member 25; D011994:Recombinant Proteins; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; C506034:Tnfrsf25 protein, mouse; C505947:Tnfsf15 protein, mouse; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000072000:NF-KappaB Inhibitor alpha