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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

  • Author Footnotes
    1 Both authors equally contributed in this project.
    Hyun-Ock Pae
    Footnotes
    1 Both authors equally contributed in this project.
    Affiliations
    Medicinal Resources Research Institute and Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug 570-749, Republic of Korea
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  • Author Footnotes
    1 Both authors equally contributed in this project.
    Gi-Su Oh
    Footnotes
    1 Both authors equally contributed in this project.
    Affiliations
    Medicinal Resources Research Institute and Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug 570-749, Republic of Korea
    Search for articles by this author
  • Bok-Soo Lee
    Affiliations
    Medicinal Resources Research Institute and Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug 570-749, Republic of Korea
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  • Joung-Sik Rim
    Affiliations
    Department of Urology, Wonkwang University School of Medicine, Iksan, Chonbug 570-749, Republic of Korea
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  • Young-Myeong Kim
    Affiliations
    Vascular System Research Center and Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chunchon, Kangwon-Do 200-701, Republic of Korea
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  • Hun-Taeg Chung
    Correspondence
    Corresponding author. Tel.: +82 63 850 6762; fax: +82 63 851 5066.
    Affiliations
    Medicinal Resources Research Institute and Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug 570-749, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 Both authors equally contributed in this project.

      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)-κB in HUVECs stimulated with tumor necrosis factor-α, 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-κB activation associated with vascular injury and inflammation in atherosclerosis.

      Abbreviations:

      ARE (antioxidant response element), CoPP (cobalt protoporphyrin), HA (3-hydroxyanthranilic acid), HO-1 (heme oxygenase-1), HUVECs (human umbilical vein endothelial cells), IDO (indoleamine 2,3-dioxygenase), I-κBα (inhibitory-κBα), MCP-1 (monocyte chemoattractant protein-1), NF-κB (transcriptional nuclear factor-κB), Nrf2 (NF-E2 related factor 2), SnPP (tin protoporphyrin), TNF-α (tumor necrosis factor-α), VCAM-1 (vascular cell adhesion molecule-1)

      Keywords

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