• Nutrition · Feb 2003

    Effect of gamma-linolenic acid or docosahexaenoic acid on tight junction permeability in intestinal monolayer cells and their mechanism by protein kinase C activation and/or eicosanoid formation.

    • Makoto Usami, Takako Komurasaki, Aki Hanada, Kaori Kinoshita, and Atsushi Ohata.
    • Division of Surgical Metabolism, Faculty of Health Science, Kobe University School of Medicine, Kobe, Japan. musa@ams.kobe-u.ac.jp
    • Nutrition. 2003 Feb 1; 19 (2): 150-6.

    ObjectivePolyunsaturated fatty acids have been characterized as immunonutrients, but the effect of gamma-linolenic acid (GLA) or docosahexaenoic acid (DHA) on intestinal permeability has rarely been reported.MethodsConfluent Caco-2 cells on porous filter were used to measure tight junction function by fluorescein sulfonic acid permeability and transepithelial electrical resistance. Treatments with 0, 10, 50, and 100 microM of GLA or DHA during 24 h were compared. Then the effects of butylated hydroxytoluene (antioxidant), 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (protein kinase C antagonist), and inhibitors of enzymatic degradation to the eicosanoids, indomethacin (cyclooxygenase inhibitor) and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone (lipoxygenase inhibitor), on GLA or DHA were examined.ResultsGLA and DHA enhanced fluorescein sulfonic acid permeability to 8.7- and 1.4-fold, respectively, and lowered transepithelial electrical resistance to 0.52- and 0.73-fold, respectively, versus the control in a concentration-dependent manner without cell injury (P < 0.001 to 0.05). Indomethacin and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone enhanced the changes mediated by GLA but did not alter the DHA effect. Butylated hydroxytoluene was ineffective. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine facilitated the changes mediated by GLA, DHA, and eicosapentaenoic acid. The results indicated that the mechanism to change tight junction permeability via protein kinase C regulation is common but that via eicosanoid formation differs among GLA, DHA, and eicosapentaenoic acid.ConclusionsGLA and DHA affect tight junction permeability in intestinal monolayer cells specifically and in a concentration-dependent manner.

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