Regular Article
Hematein Inhibits Tumor Necrotic Factor-α-Induced Vascular Cell Adhesion Molecule-1 and NF-κB-Dependent Gene Expression in Human Vascular Endothelial Cells

https://doi.org/10.1006/bbrc.2001.4480Get rights and content

Abstract

Monocyte adhesion to the endothelium via adhesion molecules is one of the earliest events in atherogenesis. It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) plays a very important role in the recruitment of monocytes in atherosclerosis. The aim of our study was to evaluate whether hematein can influence the expression of VCAM-1 and the transcription of nuclear factor-κB (NF-κB)-dependent genes. Immunohistochemistry revealed that mouse aortic artery endothelial cells express VCAM-1 after feeding a high cholesterol diet for 8 weeks. Hematein dose dependently suppressed TNF-α-induced VCAM-1 in both surface (30.8%) and soluble protein (65%) production in HUVECs. The transcription level of VCAM-1 was measured by Northern blot analysis, and decreased VCAM-1 protein expression was associated with a reduction of VCAM-1 mRNA expression. Transient transfection study of NF-κB promoter construct and electrophoretic mobility shift assay suggested that hematein inhibited both NF-κB-dependent gene expression and NF-κB activation induced by TNF-α. Our results suggest that the down-regulation of VCAM-1 expression by hematein may in part be due to the inhibition of NF-κB-dependent gene expression.

References (37)

  • A.C. van der Wal et al.

    Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions

    Am. J. Pathol.

    (1992)
  • K.D. O'Brien et al.

    Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis

    J. Clin. Invest.

    (1993)
  • G. Walker et al.

    3-Deazaadenosine prevents adhesion molecule expression and atherosclerotis lesion formation in the aortas of C57BL/6J mice

    Atheroscler. Thromb. Vasc. Boil.

    (1999)
  • S. Grimm et al.

    The inducible transcription factor NF-κB: Structure–function relationship of its protein subunits

    Biochem. J.

    (1993)
  • T. Collins et al.

    Transcriptional regulation of endothelial cell adhesion molecules: NF-κB and cytokine inducible enhancer

    FASEB J.

    (1995)
  • A.S. Neish et al.

    Functional analysis of the human vascular cell adhesion molecule 1 promoter

    J. Exp. Med.

    (1992)
  • M.F. Iademarco et al.

    Vascular cell adhesion molecule 1: Contrasting transcriptional control mechanisms in muscle and endothelium

    Proc. Natl. Acad. Sci. USA

    (1993)
  • N. Marui et al.

    Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells

    J. Clin. Invest.

    (1993)
  • Cited by (15)

    • Combination of curcumin and luteolin synergistically inhibits TNF-α-induced vascular inflammation in human vascular cells and mice

      2019, Journal of Nutritional Biochemistry
      Citation Excerpt :

      The critical roles of chemokines and adhesion molecules in the initiation and development of vascular inflammatory process and pathogenesis of CVDs have been well established [35,36]. For example, chemokine MCP-1 is essential for monocyte rolling, firm adhesion to ECs and the subsequent transmigration into vascular tissue [37,39,46] and adhesion molecules such as ICAM-1, VCAM-1, and E-selectin play a pivotal role in attracting, binding and transmigrating monocytes into sites of inflammation [38,47]. These have been confirmed by that mice lacking receptors for these molecules are less susceptible to vascular disease and have fewer monocytes in vascular lesions [39].

    • Pterostilbene exerts an anti-inflammatory effect via regulating endoplasmic reticulum stress in endothelial cells

      2016, Cytokine
      Citation Excerpt :

      Therefore, in this study, we chose TNF-α as an agent to induce inflammatory responses in endothelial cells. Additionally, IL-8 and MCP-1, the key chemokines that play regulatory roles in the interactions between monocytes and endothelial cells and in the migration of monocytes into vessels [26], were chosen as inflammatory markers. Adhesion molecules have also been identified as atherosclerotic inflammatory markers, including MMP9, ICAM1 and E-selectin [10,20].

    • Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IKBα/NF-κB signaling pathway

      2015, Journal of Nutritional Biochemistry
      Citation Excerpt :

      In addition to chemokines, adhesion molecules such as ICAM-1, VCAM-1 and E-selectin also play a pivotal role in attracting, binding and transmigrating monocytes into sites of inflammation [41]. In fact, these adhesion molecules are considered atherosclerotic inflammatory markers [42,43], which are increased in advanced human coronary atherosclerotic plaques as well as in experimental models of atherosclerosis [42,43]. In this study, our data showed that luteolin treatment remarkably suppressed TNF-α-induced expression of MCP-1, VCAM-1 and ICAM-1 in cultured ECs.

    • Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway

      2014, Journal of Nutritional Biochemistry
      Citation Excerpt :

      Indeed, MCP-1 is found in human atheroma, and mice lacking a MCP-1 receptor are found to be less susceptible to atherosclerosis [44]. The adhesion molecules ICAM-1, VCAM-1 and E-selectin are known atherosclerotic inflammatory markers [45,46], which are largely increased in advanced human coronary atherosclerotic plaques, as well as in experimental models of atherosclerosis[45,46]. Also, these adhesion molecules are widely expressed in ECs.

    • Genistein inhibits TNF-α-induced endothelial inflammation through the protein kinase pathway A and improves vascular inflammation in C57BL/6 mice

      2013, International Journal of Cardiology
      Citation Excerpt :

      Cytokines such as TNF-α induces the expression of adhesion molecules on the cell surface of ECs resulting in the adhesion and migration of monocytes to the subendothelial space [3]. The adhesion molecules such as ICAM-1, VCAM-1, and E-selectin have been suggested to be atherosclerotic inflammatory markers [59,60]. Indeed, previous studies have demonstrated increased expression of these endothelium-derived adhesion molecules in advanced human coronary atherosclerotic plaques as well as in experimental models of atherosclerosis [59,60].

    View all citing articles on Scopus
    1

    To whom correspondence should be addressed at Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusong, Taejon 305-600, Korea. Fax: +82-42-860-4609. E-mail: [email protected].

    View full text