Severe Anemia Caused by Multiple Intestinal Helminth Infestation

Abstract

simvastatin-induced (5 mM, 16 hours) Rac activation was markedly attenuated in ECs transfected with siRNA specific for integrin b4 (38% decrease), with no change in total Rac noted. Additionally, LPSinduced (5 mg/mL, 10 minutes) Erk phosphorylation was inhibited in ECs treated with simvastatin (5 mM, 16 hours), an effect that may contribute to the antiangiogenic properties of statins, whereas Erk phosphorylation was significantly enhanced in ECs transfected with integrin b4 siRNA (100% increase). Finally, RT-PCR confirmed that IL-8 RNA was markedly increased in integrin b4-silenced ECs compared with control cells (<threefold increase), whereas LPS-induced (5 mg/mL, 10 minutes) IL-8 expression was significantly attenuated in simvastatin-treated (5 mM, 16 hours) ECs compared with LPS alone (30% decrease), findings that may account for the anti-inflammatory properties of statins. Our results indicate a novel regulatory mechanism of Rac and Erk activities and the expression of IL-8 in ECs that is mediated by integrin b4. These data advance our understanding of the complex effects of statins on EC signaling and may ultimately lead to the identification of novel clinical targets.