A GATA‐specific inhibitor (K‐7174) rescues anemia induced by IL‐1β, TNF‐α, or l ‐NMMA

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Abstract
SPECIFIC AIMOne common pathogenesis of anemia of chronic diseases (ACD) and with renal disease appears to be stimulation of GATA binding activity by interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), or NG-monomethyl l-arginine (L-NMMA), which inhibits erythropoietin (Epo) promoter activity. We investigated the ability of K-7174 (a GATA-specific inhibitor) to improve Epo production after inhibition by IL-1β, TNF-α, or L-NMMA treatment in Hep3B cells in vitro and in an in vivo mouse assay.PRINCIPAL FINDINGS1. Epo protein production, which is inhibited by IL-1β or TNF-α, is rescued by K-7174Hypoxia (1% O2) induced Epo protein production from aliquots of 3 × 106 Hep3B cells over 24 h. However, 15 U/mL IL-1β and 220 U/mL TNF-α each inhibited Epo protein production, and addition of 10–20 μM K-7174 rescued these inhibitions in a dose-dependent manner (Fig. 1⤻ ). Figure 1.Effects of different doses of K-7174 on the inhibition of Epo protein production from Hep3B cells by IL-1β and TNF-α. Aliquots of 3 × 10...