Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production

Wolfgang Jelkmann; Thomas Hellwig-Buergel

doi:10.1016/S0301-472X(98)00054-X

Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production

Wolfgang Jelkmann^*, Thomas Hellwig-Buergel

^*Corresponding author for this work

Institute of Physiology

13 Citations (Scopus)

Abstract

Tumor necrosis factor α (TNFα) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RH) receptor is responsible for the TNFα-induced inhibition of hepatic Epo synthesis. When the effects of two receptor-specific mutants were compared, only the TNF-RI-specific isoform proved to suppress the formation of immunoreactive Epo in the human hepatoma cell lines HepG2 and Hep3B, similar to the effect of wild-type TNFα. Anti-TNFα antibody restored Epo production in TNFα- or TNF-RI mutant-treated cultures. By gel shift assay NF-κB binding to DNA was demonstrated following the addition of TNFα or TNF-RI-specific mutant to HepG2 cells, while the TNF-RII-specific mutant was ineffective. Finally, immunoreactive TNF-RI, but not TNF-RII, fragments were measurable in cell culture supernatants. Taken together, these results suggest that the inhibition of hepatic Epo production by TNFα is mediated by TNF-RI signaling.

Original language	English
Journal	Experimental Hematology
Volume	27
Issue number	2
Pages (from-to)	224-228
Number of pages	5
ISSN	0301-472X
DOIs	https://doi.org/10.1016/S0301-472X(98)00054-X
Publication status	Published - 02.1999

Funding

The authors are indebted to Dr. W. Lesslauer and Dr. H. Loetscher (F. Hoffmann-La Roche Ltd., Basel, Switzerland) for the supply of TNF receptor-specific mutants. The study was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 367-C8).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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10.1016/S0301-472X(98)00054-X

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title = "Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production",

abstract = "Tumor necrosis factor α (TNFα) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RH) receptor is responsible for the TNFα-induced inhibition of hepatic Epo synthesis. When the effects of two receptor-specific mutants were compared, only the TNF-RI-specific isoform proved to suppress the formation of immunoreactive Epo in the human hepatoma cell lines HepG2 and Hep3B, similar to the effect of wild-type TNFα. Anti-TNFα antibody restored Epo production in TNFα- or TNF-RI mutant-treated cultures. By gel shift assay NF-κB binding to DNA was demonstrated following the addition of TNFα or TNF-RI-specific mutant to HepG2 cells, while the TNF-RII-specific mutant was ineffective. Finally, immunoreactive TNF-RI, but not TNF-RII, fragments were measurable in cell culture supernatants. Taken together, these results suggest that the inhibition of hepatic Epo production by TNFα is mediated by TNF-RI signaling.",

author = "Wolfgang Jelkmann and Thomas Hellwig-Buergel",

note = "Funding Information: The authors are indebted to Dr. W. Lesslauer and Dr. H. Loetscher (F. Hoffmann-La Roche Ltd., Basel, Switzerland) for the supply of TNF receptor-specific mutants. The study was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 367-C8). Copyright: Copyright 2007 Elsevier B.V., All rights reserved.",

year = "1999",

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doi = "10.1016/S0301-472X(98)00054-X",

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pages = "224--228",

journal = "Experimental Hematology",

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T1 - Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production

AU - Jelkmann, Wolfgang

AU - Hellwig-Buergel, Thomas

N1 - Funding Information: The authors are indebted to Dr. W. Lesslauer and Dr. H. Loetscher (F. Hoffmann-La Roche Ltd., Basel, Switzerland) for the supply of TNF receptor-specific mutants. The study was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 367-C8). Copyright: Copyright 2007 Elsevier B.V., All rights reserved.

PY - 1999/2

Y1 - 1999/2

N2 - Tumor necrosis factor α (TNFα) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RH) receptor is responsible for the TNFα-induced inhibition of hepatic Epo synthesis. When the effects of two receptor-specific mutants were compared, only the TNF-RI-specific isoform proved to suppress the formation of immunoreactive Epo in the human hepatoma cell lines HepG2 and Hep3B, similar to the effect of wild-type TNFα. Anti-TNFα antibody restored Epo production in TNFα- or TNF-RI mutant-treated cultures. By gel shift assay NF-κB binding to DNA was demonstrated following the addition of TNFα or TNF-RI-specific mutant to HepG2 cells, while the TNF-RII-specific mutant was ineffective. Finally, immunoreactive TNF-RI, but not TNF-RII, fragments were measurable in cell culture supernatants. Taken together, these results suggest that the inhibition of hepatic Epo production by TNFα is mediated by TNF-RI signaling.

AB - Tumor necrosis factor α (TNFα) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RH) receptor is responsible for the TNFα-induced inhibition of hepatic Epo synthesis. When the effects of two receptor-specific mutants were compared, only the TNF-RI-specific isoform proved to suppress the formation of immunoreactive Epo in the human hepatoma cell lines HepG2 and Hep3B, similar to the effect of wild-type TNFα. Anti-TNFα antibody restored Epo production in TNFα- or TNF-RI mutant-treated cultures. By gel shift assay NF-κB binding to DNA was demonstrated following the addition of TNFα or TNF-RI-specific mutant to HepG2 cells, while the TNF-RII-specific mutant was ineffective. Finally, immunoreactive TNF-RI, but not TNF-RII, fragments were measurable in cell culture supernatants. Taken together, these results suggest that the inhibition of hepatic Epo production by TNFα is mediated by TNF-RI signaling.

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M3 - Journal articles

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AN - SCOPUS:0033001379

SN - 0301-472X

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ER -

Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production

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