3-Hydroxyanthranilic acid, one of L-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells.

Abstract

Heme oxygenase (HO)-1 is important in the vascular system, and its genetic or pharmacological induction in endothelium would be effective for the prevention and treatment of atherosclerosis. The naturally occurring antioxidant 3-hydroxyanthranilic acid (HA), one of l-tryptophan metabolites formed in vivo along the metabolic route known as the kynurenine pathway during inflammation or infection, was found to induce HO-1 expression and to stimulate nuclear translocation of NF-E2 related factor 2 (Nrf2) in human umbilical vein endothelial cells (HUVECs). Pre-treatment with HA inhibited the secretion of monocyte chemoattractant protein (MCP)-1, the expression of vascular cell adhesion molecule (VCAM)-1 and the activation of transcriptional nuclear factor (NF)-kappaB in HUVECs stimulated with tumor necrosis factor-alpha, the major pro-inflammatory cytokine causing endothelial inflammation. Interestingly, the observed anti-inflammatory effects of HA were mimicked by a HO-1 inducer, cobalt protoporphyrin, and bilirubin, one of HO-1 enzymatic products, but abolished in the presence of a HO-1 inhibitor, tin protoporphyrin. Based on our findings, we suggest that Nrf2-dependent HO-1 expression induced by HA inhibits MCP-1 secretion, VCAM-1 expression and NF-kappaB activation associated with vascular injury and inflammation in atherosclerosis.

• Authors: Hyun-Ock Pae, Gi-Su Oh, Bok-Soo Lee, Joung-Sik Rim, Young-Myeong Kim, Hun-Taeg Chung
• Journal: Atherosclerosis (Atherosclerosis) Vol. 187 Issue 2 Pg. 274-84 (Aug 2006) ISSN: 0021-9150 [Print] Ireland
• PMID: 16246346 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• CCL2 protein, human
• Chemokine CCL2
• Free Radical Scavengers
• NF-E2-Related Factor 2
• NF-kappa B
• NFE2L2 protein, human
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• 3-Hydroxyanthranilic Acid
• Tryptophan
• Heme Oxygenase-1
• Bilirubin

Topics

• 3-Hydroxyanthranilic Acid (metabolism, pharmacology)
• Antioxidants (metabolism)
• Atherosclerosis (immunology, metabolism)
• Bilirubin (metabolism, pharmacology)
• Chemokine CCL2 (metabolism)
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Free Radical Scavengers (metabolism, pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Response Elements (physiology)
• Tryptophan (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Umbilical Veins (cytology)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)