What question did this study set out to answer?

To determine whether the 55-kDa TNF receptor (TNF-R1) is required and sufficient to drive TNF-induced cytotoxicity, apoptosis, and acute liver failure.

February 1, 1995The Journal of ImmunologyOpen Access

Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release.

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Authors

MLMarcel LeistUniversity of Messina FGFlorian GantnerBoehringer Ingelheim (Germany)SJS JilgUniversity of Konstanz

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Implication

Experimental study reveals 55-kDa TNF receptor mediates apoptosis and liver failure in murine hepatocytes, indicating TNF-R1 is necessary and sufficient for septic liver injury.

Key Points

To determine whether the 55-kDa TNF receptor (TNF-R1) is required and sufficient to drive TNF-induced cytotoxicity, apoptosis, and acute liver failure.
Treated primary hepatocyte cultures from wild-type C57BL and TNF-R1-deficient mice with huTNF-alpha, huTNF-beta, and muTNF-alpha to assess cytotoxicity, DNA fragmentation, and gene induction.
Evaluated hepatotoxicity, DNA fragmentation, and acute liver failure in vivo using D-galactosamine-sensitized wild-type versus TNF-R1-deficient mice.
In wild-type hepatocytes, TNF variants (> 1 ng/ml) elicited cytotoxicity, oligonucleosomal DNA fragmentation, nitric oxide synthase induction, and serum amyloid A secretion.
Hepatocytes lacking TNF-R1 showed complete absence of cytotoxicity, DNA fragmentation, or inflammatory responses, even at TNF concentrations exceeding 1 µg/ml.
In vivo challenge caused fatal liver failure and DNA fragmentation in D-galactosamine-sensitized wild-type mice, while TNF-R1-deficient mice were completely protected.

Cite This Study

Leist et al. (1995) studied this question.

synapsesocial.com/papers/6a71d31c5671bbf00bc2f6aa https://doi.org/10.4049/jimmunol.154.3.1307

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Implication

Experimental study reveals 55-kDa TNF receptor mediates apoptosis and liver failure in murine hepatocytes, indicating TNF-R1 is necessary and sufficient for septic liver injury.

Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release.

Discussion

Member takes

Implication

Key Points

Cite This Study

Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release.

Discussion

Member takes

Implication

Key Points

Cite This Study

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