Sodium phenyl butyrate downregulates endothelin-1 expression in cultured human endothelial cells: relevance to sickle-cell disease.
As hydroxyurea (HU), sodium phenyl butyrate (SPB) is known to induce fetal hemoglobin (HbF) expression and thus shows potentials for sickle-cell disease (SCD) treatment. More recently, few studies suggested that endothelial cells (ECs), a major pathophysiological actor of SCD, are also a target of SPB. Here, we show that SPB, as HU, reduces endothelin-1 mRNA expression and peptide release by human ECs in culture. SPB increases VCAM-1 and ICAM-1 mRNAs and soluble ICAM-1 release. Both drugs have a cumulative effect on ICAM-1 expression. We conclude that SPB, as HU, also affects the expression of molecules important to the pathophysiology of SCD, in addition to its effect on HbF. Its potential as an alternative or adjuvant drug in SCD treatment warrants further investigations.
Odièvre
Marie-Hélène
MH
Inserm, U763, Hôpital Robert Debré, Paris F-75019, France.
Brun
Manuel
M
Krishnamoorthy
Rajagopal
R
Lapouméroulie
Claudine
C
Elion
Jacques
J
D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000503:physiopathology; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D010654:Phenylbutyrates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D019332:Endothelin-1; D010654:Phenylbutyrates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C075773:4-phenylbutyric acid; D007371:Interferon-gamma; D006918:Hydroxyurea