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

Overexpression of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF alpha), has been implicated in the pathogenesis of anaemia of inflammation. TNF alpha suppresses erythroid colony formation via both direct and indirect effects on haematopoietic progenitors, often involving activation of nuclear factor (NF-kappa B 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 TNF alpha-mediated suppression of erythropoiesis in human CD34(+) haematopoietic progenitors. We found that resveratrol partially reverses the erythroid suppressive effects of TNF alpha, leading to significant recovery in burst forming unit-erythroid colony formation in human CD34(+) cells. CD34(+) cells preincubated with resveratrol for 72 h in the presence of TNF alpha inhibited NF-kappa B activation via decreased NF-kappa B nuclear localization without altering total NF-kappa B protein levels and independent of I kappa B degradation. Resveratrol also significantly restored the baseline expression of erythroid transcription factors NFE2 and the GATA1/GATA2 ratio in CD34(+) cells treated with TNF alpha. In conclusion, resveratrol may inhibit TNF alpha-mediated NF-kappa B activation and promote erythropoiesis in primary human CD34(+) cells.