Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production
Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production
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DOI：
10.1016/s0301-472x(98)00054-x
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发表时间：
1999-02-01
影响因子：
2.6
通讯作者：
Hellwig-Buergel, T
中科院分区：
文献类型：
--
作者：
Jelkmann, W;Hellwig-Buergel, T
肿瘤坏死因子α（TNF α）被认为与炎症性疾病中促红细胞生成素（Epo）产生的钝化有关。本研究旨在探讨55 kD（TNF-RI）或75 kD（TNF-RU）受体是否参与TNF α诱导的肝Epo合成抑制。当两种受体特异性突变体的作用进行比较时，只有TNF-RI特异性同种型被证明能抑制人肝癌细胞系HepG 2和Hep 3B中免疫反应性Epo的形成，与野生型TNF α的作用相似。抗TNF α抗体可恢复TNF α或TNF-RI突变体处理的培养物中Epo的产生。通过凝胶迁移试验，证明在加入TNF α或TNF-RI特异性突变体后，NF-κ B B与DNA结合，而TNF-RII特异性突变体则无效。最后，免疫反应性TNF-RI，但不是TNF-RII，片段在细胞培养上清液中可测量。总之，这些结果表明TNF α对肝Epo产生的抑制是由TNF-RI信号传导介导的。(C)1999年国际实验血液学学会，由Elsevier Science Inc.出版。
Tumor necrosis factor alpha (TNF alpha) 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-RU) receptor is responsible for the TNF alpha-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 TNF alpha. Anti-TNF alpha antibody restored Epo production in TNF alpha- or TNF-RI mutant-treated cultures, By gel shift assay NF-kappa B binding to DNA was demonstrated following the addition of TNF alpha 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 TNF alpha is mediated by TNF-RI signaling. (C) 1999 International Society for Experimental Hematology, Published by Elsevier Science Inc.