title: Resveratrol ameliorates TNFα-mediated suppression of erythropoiesis in human CD34(+) cells via modulation of NF-κB signalling.
abstract: Overexpression of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFα), has been implicated in the pathogenesis of anaemia of inflammation. TNFα suppresses erythroid colony formation via both direct and indirect effects on haematopoietic progenitors, often involving activation of nuclear factor (NF)-κB signalling resulting in downregulation of transcription factors critical for erythropoiesis. There is a dearth of effective and safe therapies for many patients with inflammatory anaemia. Resveratrol is a flavanol found in red wine grapes that possesses potent anti-inflammatory properties, but studies of its impact on human erythropoiesis have proven contradictory. We investigated whether resveratrol ameliorates TNFα-mediated suppression of erythropoiesis in human CD34(+) haematopoietic progenitors. We found that resveratrol partially reverses the erythroid suppressive effects of TNFα, leading to significant recovery in burst forming unit-erythroid colony formation in human CD34(+) cells. CD34(+) cells pre-incubated with resveratrol for 72 h in the presence of TNFα inhibited NF-κB activation via decreased NF-κB nuclear localization without altering total NF-κB protein levels and independent of IκB degradation. Resveratrol also significantly restored the baseline expression of erythroid transcription factors NFE2 and the GATA1/GATA2 ratio in CD34(+) cells treated with TNFα. In conclusion, resveratrol may inhibit TNFα-mediated NF-κB activation and promote erythropoiesis in primary human CD34(+) cells.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
authors.forename: Jee-Yeong
authors.initials: JY
authors.lastname: Jeong
authors.forename: Matthew
authors.initials: M
authors.lastname: Silver
authors.forename: Aric
authors.initials: A
authors.lastname: Parnes
authors.forename: Sarah
authors.initials: S
authors.lastname: Nikiforow
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Vanasse
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015672:Erythroid Precursor Cells / Q000187:drug effects; D050981:Erythroid-Specific DNA-Binding Factors / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018952:Antigens, CD34; D050981:Erythroid-Specific DNA-Binding Factors; D016328:NF-kappa B; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000077185:Resveratrol