Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney.
Bacterial endotoxin (LPS) is responsible for much of the widespread inflammatory response seen in sepsis, a condition often accompanied by acute renal failure (ARF). In this work we report that mice deficient in TNFR1 (TNFR1(-/-)) were resistant to LPS-induced renal failure. Compared with TNFR1(+/+) controls, TNFR1(-/-) mice had less apoptosis in renal cells and fewer neutrophils infiltrating the kidney following LPS administration, supporting these as mediators of ARF. TNFR1(+/+) kidneys transplanted into TNFR1(-/-) mice sustained severe ARF after LPS injection, which was not the case with TNFR1(-/-) kidneys transplanted into TNFR1(+/+) mice. Therefore, TNF is a key mediator of LPS-induced ARF, acting through its receptor TNFR1 in the kidney.
Cunningham
Patrick N
PN
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. pcunning@medicine.bsd.uchicago.edu
Dyanov
Hristem M
HM
Park
Pierce
P
Wang
Jun
J
Newell
Kenneth A
KA
Quigg
Richard J
RJ
D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis; D019446:Endotoxemia / Q000150:complications*; D007668:Kidney / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015703:Antigens, CD; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse