Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation
作者： Miguel P Soares , Mark P Seldon , Isabel Pombo Gregoire , Tatiana Vassilevskaia , Pascal O Berberat
DOI: 10.4049/JIMMUNOL.172.6.3553
关键词:
摘要: Heme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted bilirubin. Heme-derived Fe2+ induces expression iron-sequestering protein ferritin activates ATPase Fe2+-secreting pump, decrease intracellular free content. Based on antioxidant effect bilirubin that decreased cellular we questioned whether HO-1 would modulate proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for E-selectin (CD62), ICAM-1 (CD54), VCAM-1 (CD106). found overexpression in EC inhibited TNF-alpha-mediated VCAM-1, but not expression, as at RNA level. Heme-driven had similar effects to those overexpressed HO-1. In addition, activation NF-kappaB, a transcription factor required up-regulation these EC. Bilirubin and/or chelation mimicked HO-1, whereas biliverdin or monoxide did not. conclusion, inhibits via mechanism inhibition NF-kappaB This mediated by probably monoxide.
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