TL1A both promotes and protects from renal inflammation and injury

Al-Lamki, Rafia S., Wang, Jun, Tolkovsky, Aviva M., Bradley, J. Andrew, Griffin, Jules L., Thiru, Sathia, Wang, Edward Chung Yern ORCID: https://orcid.org/0000-0002-2243-4964, Bolton, Eleanor, Min, Wang, Moore, Paul, Pober, Jordan S. and Bradley, John R. 2008. TL1A both promotes and protects from renal inflammation and injury. Journal of the American Society of Nephrology 19 (5) , pp. 953-960. 10.1681/ASN.2007060706

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Abstract

Death receptor 3 (DR3), a member of the TNF receptor (TNFR) superfamily, is induced in human renal tubular epithelial cells (TEC) in response to injury. This study examined the expression and actions of TL1A, the principal ligand for DR3. In histologically normal tissue from biopsy or nephrectomy specimens of renal allografts, TL1A mRNA and protein were expressed in vascular endothelial cells but not in TEC. In specimens of acute or antibody-mediated allograft rejection, vascular endothelial cells and infiltrating leukocytes expressed increased TL1A mRNA and protein, but TEC expressed TL1A protein without mRNA, consistent with uptake of exogenous ligand. Addition of TL1A to organ cultures of human or mouse kidney caused activation of NF-kappaB, expression of TNFR2, activation of caspase-3, and apoptosis in TEC. Inhibition of NF-kappaB activation increased TL1A-mediated caspase-3 activation and apoptosis of TEC, but it did not reduce the induction of TNFR2. In organ culture of DR3-deficient mouse kidneys, addition of TL1A induced TNFR2 but did not activate NF-kappaB and did not increase apoptosis of TEC. These data suggest that TL1A may contribute to renal inflammation and injury through DR3-mediated activation of NF-kappaB and caspase-3, respectively, but that an unidentified receptor may mediate the NF-kappaB-independent induction of TNFR2 in TEC.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Lippincott, Williams & Wilkins
ISSN:	1046-6673
Last Modified:	20 Oct 2022 08:54
URI:	https://orca.cardiff.ac.uk/id/eprint/30021

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