Tumor necrosis factor (TNF)-alpha directly inhibits human erythropoiesis in vitro: role of p55 and p75 TNF receptors

Abstract

Two tumor necrosis factor receptors (TNFRs) with molecular weights of 55 kD (TNFR-p55) and 75 kD (TNFR-p75) have recently been identified and cloned. In previous studies, TNFR-p55 has been shown to exclusively mediate bidirectional effects of TNF-alpha on committed bone marrow granulocyte-macrophage progenitor cells, whereas both TNFR-p55 and TNFR- p75 can mediate inhibition of primitive progenitors requiring multiple cytokines to proliferate. We show here that TNF-alpha potently and directly inhibits the in vitro growth of committed erythroid progenitor cells in response to multiple cytokine combinations, and that TNF-alpha- induced inhibition of burst-forming unit-erythroid colony formation is mainly mediated through TNFR-p55, although TNFR-p75-mediated inhibition could be observed on progenitors responsive to erythropoietin alone. Moreover, at low TNF-alpha concentrations (2 ng/mL), TNF-alpha stimulates interleukin-3-dependent in vitro growth of committed granulocyte-macrophage progenitor cells, whereas it potently inhibits erythroid progenitor cell proliferation, showing that one concentration of TNF-alpha can simultaneously and bidirectionally modulate interleukin-3-dependent growth of committed granulocyte-macrophage (stimulation) and erythroid progenitor cells (inhibition).

Tumor Necrosis Factor Alpha Enhances the Adenoviral Transduction of CD34+Hematopoietic Progenitor Cells

“…However, it is possible that the anti-TNFR2-TNFR complex may induce the uptake of adenoviral particles by an unidentified mechanism, thereby preventing a complete inhibition of the TNF-α-dependent increase of the adenoviral transduction efficiency. This TNFR neutralization study is also consistent with previous publications showing that TNF receptor I is responsible for all in vitro growth-related effects on more committed human bone marrow progenitor cells [13], while TNF receptor II is directly involved in signaling growth inhibition in the most primitive human and murine stem cells [14].…”

Resveratrol ameliorates TNFα‐mediated suppression of erythropoiesis in human CD34+ cells via modulation of NF‐κB signalling

“…Consistent with this latter postulate, tumour necrosis factor alpha (TNFα), as well as other pro‐inflammatory cytokines (Roubenoff et al , 1998; Ershler & Keller, 2000; Bruunsgaard, 2002; Bruunsgaard & Pedersen, 2003; Krabbe et al , 2004; Ferrucci et al , 2005), may directly suppress erythropoiesis by signalling through TNFα receptors expressed on haematopoietic progenitors (Rusten & Jacobsen, 1995). Although TNFα has been demonstrated to inhibit erythroid differentiation of K562, HEL and TF1 cells through activation of p38 mitogen‐activated protein kinase (MAPK) signalling pathways and regulation of erythroid specific transcriptional factors, including GATA binding factor‐1 ( GATA1 ), GATA binding factor‐2 ( GATA2 ) and zinc finger protein, multi‐type 1 [ ZFPM1 , previously termed friend of GATA1 ( FOG1 )] (Buck et al , 2008), a detailed understanding of the mechanisms by which TNFα suppresses erythroid differentiation and proliferation of primary human haematopoietic progenitors remains elusive.…”

Recombinant Protein of Variola Virus Abolishes the Effects of Tumor Necrosis Factor Upon Marrow Hematopoiesis in Balb/С Mice

“…Нами показано, что rmTNF оказывает ингибирующий эффект на эритроидное колониеобразование. Ранее было продемонстрировано снижение количества эритроидных колоний под влиянием TNF in vitro [28]; цитокин также ингибировал эритроидное колониеобразование (БОЕ-Э и КОЕ-Э) различными клеточными линиями (К562, HL60, HEL) [27]. Показан супрессивный эффект TNF на пролиферативную активность гликофорин-положительных (GPA + ) эритроидных клеток [34].…”