Pro-inflammatory proteins S100A9 and TNF α suppress erythropoietin elaboration in myelodysplastic syndromes.

Pro-inflammatory proteins S100A9 and TNFα suppress erythropoietin elaboration in myelodysplastic syndromes. Haematologica. 2017 Oct 05;: Authors: Cluzeau T, McGraw KL, Irvine B, Masala E, Ades L, Basiorka AA, Maciejewski JP, Auberger P, Wei S, Fenaux P, Santini V, List A Abstract Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating TNFα and IL-1β production. The role of MDS-related inflammatory proteins in endogenous Epo regulation and response to erythroid stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro Epo elaboration. Serum collected from 311 MDS patients were investigated (125 prior to erythroid stimulating agents and 186 prior to lenalidomide). Serum concentrations of S100A9, S100A8, TNFα, IL1β and Epo were analyzed by ELISA. Using Epo-producing HepG2 cells, we show that S100A9, TNFα and IL-1β suppress transcription and cellular elaboration of Epo. Pre-incubation with lenalidomide significantly diminished suppression of Epo production by S100A9 or TNFα. Moreover, in myelodysplastic syndromes peripheral blood mononuclear cells, lenalidomide significantly reduced steady state S100A9 generation (p=0.01) and LPS-induced TNFα elaboration (p=0.002). ELISA analysis of serum from 316 non-del(5q) myel...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research