TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=0033001379&partnerID=8YFLogxK
U2 - 10.1016/S0301-472X(98)00054-X
DO - 10.1016/S0301-472X(98)00054-X
M3 - Journal articles
C2 - 10029160
AN - SCOPUS:0033001379
SN - 0301-472X
VL - 27
SP - 224
EP - 228
JO - Experimental Hematology
JF - Experimental Hematology
IS - 2
ER -
