The role of haem oxygenase-1 in the decrease of endothelial intercellular adhesion molecule-1 expression by curcumin

Basic Clin Pharmacol Toxicol. 2007 Dec;101(6):411-5. doi: 10.1111/j.1742-7843.2007.00151.x. Epub 2007 Oct 31.

Abstract

Intercellular adhesion molecule-1 (ICAM-1) is involved in neutrophil transmigration across endothelium during sepsis-induced acute lung injury and anti-ICAM-1 interventions may represent new strategy of pulmonary protection. Haem oxygenase-1 (HO-1) has been demonstrated to exert anti-inflammatory actions via decrease of expression of adhesion molecules. We investigated the role of HO-1 in the action of curcumin, a naturally occurring yellow pigment isolated from plant Curcuma longa L., on ICAM-1 expression in tumour necrosis factor-alpha-stimulated EA.hy926 cells and lungs of lipopolysaccharide-treated mice. Both, in vitro and in vivo curcumin induced HO-1 and curcumin-elicited induction of HO-1 was associated with inhibition ICAM-1 expression. Moreover, curcumin significantly inhibited pulmonary sequestration of leucocytes in response to lipopolysaccharide as evidenced by decrease of myeloperoxidase activity in lung tissue. Both in vitro and in vivo effects of curcumin were reversed by an inhibitor of HO activity, chromium (III) mesoporphyrin IX chloride. We conclude that induction of HO-1, via decrease of endothelial ICAM-1, plays a pivotal role in curcumin-dependent prevention of pulmonary sequestration of neutrophils in a mouse model of endotoxaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Curcuma / chemistry
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endotoxemia / drug therapy
  • Female
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / drug effects*
  • Intercellular Adhesion Molecule-1 / genetics
  • Lipopolysaccharides
  • Lung / drug effects
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Peroxidase / drug effects
  • Peroxidase / metabolism
  • Random Allocation
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects*

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Peroxidase
  • Heme Oxygenase-1
  • Curcumin