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

Wolfgang Jelkmann*, Thomas Hellwig-Buergel

*Korrespondierende/r Autor/-in für diese Arbeit
13 Zitate (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.

OriginalspracheEnglisch
ZeitschriftExperimental Hematology
Jahrgang27
Ausgabenummer2
Seiten (von - bis)224-228
Seitenumfang5
ISSN0301-472X
DOIs
PublikationsstatusVeröffentlicht - 02.1999

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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