Regular Article
Regulation of Tight Junction Permeability and Occludin Expression by Polyunsaturated Fatty Acids

https://doi.org/10.1006/bbrc.1998.8288Get rights and content

Abstract

Tight junctions (TJ) are the topical most structure in epithelial and endothelial cells and play a key role in the control of permeability and prevention of tumour cell invasion of endothelium. In this study we examined the effects of a range of polyunsaturated fatty acids on the function of TJs and the expression of occludin, a key molecule in the TJs of the human vascular endothelial cell line, ECV304. Treatment of the endothelial cells with gamma linolenic acid, an anti-cancer PUFA, increased the transendothelial cell resistance (TER) and reduced the paracellular permeability to large molecules. The effects were seen without any changes in the viability of the endothelial cells. Occludin, a recently identified molecule, which plays a major role in tight junctions was up-regulated by this fatty acid as revealed by both Western blotting and immunofluorescence. Other fatty acids were also tested. Eicosapentaenoic acid (EPA) also exerted an up-regulatory effect, but LA and AA down-regulated the expression. We conclude that GLA and EPA which also have other anti-cancer effects, regulate the expression of occludin in endothelial cells and thus contribute to the modification of the TER of these cells.

References (33)

  • H. Satoh et al.

    Exp. Cell Res.

    (1996)
  • W.G. Jiang et al.

    Biochem Biophys Res Commun.

    (1997)
  • J. Kramar et al.

    J. Nutr.

    (1953)
  • P.L. Woo et al.

    J. Biol. Chem.

    (1996)
  • J.M. Staddon et al.

    Curr. Opinion Neurobiology.

    (1996)
  • N. Utoguchi et al.

    Cancer Lett.

    (1995)
  • J.M. Anderson et al.

    Am. J. Physiol.

    (1995)
  • S. Tsukita et al.

    Cell Structure Function

    (1996)
  • S. Citi

    J Cell Biol.

    (1993)
  • M. Furuse et al.

    J. Cell Biol.

    (1993)
  • M. Furuse et al.

    J. Cell Biol.

    (1994)
  • M. Furuse et al.

    J. Cell Sci.

    (1996)
  • K.M. McCarthy et al.

    J. Cell Sci.

    (1996)
  • M.S. Balda et al.

    J. Cell Biol.

    (1996)
  • R.O. Stuart et al.

    Proc. Natl. Acad. Sci. U.S.A.

    (1995)
  • T. Yamamoto et al.

    J. Cell Biol.

    (1997)
  • Cited by (111)

    • Omega-3 polyunsaturated fatty acids alleviate hydrogen sulfide-induced blood-testis barrier disruption in the testes of adult mice

      2020, Reproductive Toxicology
      Citation Excerpt :

      A recent study demonstrated that the supply of ω-3 PUFAs ameliorated testicular effects in Fads2-deficient mice by replacing the deficiency and inducing the reconstruction of the BTB [27]. In addition, numerous investigations have indicated that ω-3 PUFAs can upregulate the TJ proteins impaired by multiple toxicants in the intestinal mucosal barrier [28,29], blood-brain barrier [30] and tumor epithelial and endothelial cells [31]. Therefore, we hypothesized that ω-3 PUFAs might be useful for the improvement of BTB dysfunction in our present study.

    View all citing articles on Scopus

    Horrobin, D. F.

    View full text