Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute Kidney Injury / etiology*
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Animals
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Antigens, CD / physiology*
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Apoptosis
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Endotoxemia / complications*
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Kidney / pathology
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Inbred C57BL
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Neutrophils / drug effects
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase Type II
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Receptors, Tumor Necrosis Factor / physiology*
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Antigens, CD
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Lipopolysaccharides
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor-alpha
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse