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Linoleic Acid, but not Oleic Acid, Upregulates Production of lnterleukin-8 by Human Vascular Smooth Muscle Cells via Arachidonic Acid Metabolites Under Conditions of Oxidative Stress

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Abstract

Objective

Preeclampsia is associated with oxidative stress, elevated plasma levels of linoleic acid (LA), and increased vascular smooth muscle expression of the inflammatory chemokine, interleukin-8 (IL-8). We hypothesized that increased levels of LA under conditions of oxidative stress would increased production of IL-8 by vascular smooth muscle cells because LA is the dietary precursor to arachidonic acid (AA) and its metabolites that mediate inflammation. We also hypothesized that oleic acid (OA), which is not metabolized to AA metabolites, would not increase IL-8 under conditions of oxidative stress.

Methods

To test this hypothesis, we cultured placental arterial smooth muscle (PASM) cells with an oxidizing solution enriched with LA (OxLA) or OA (OxOA). Media concentrations were analyzed for IL-8 and AA metabolites. Inhibitors were used to block the lipoxygenase and cyclooxygenase pathways.

Results

Exposure of cells to OxLA, but not to OxOA, significantly increased production of IL-8. OxLA also significantly increased production of AA metabolites. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, blocked IL-8 and leukotriene B4 (LTB4) production induced by OxLA, whereas indomethacin, an inhibitor of the cyclooxygenase pathway, blocked LL-8, prostaglandin E2 (PGE2), and thromboxane B2 (TXBJ production. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated gene expression in PASM cells for representative lipoxygenase (LTB4) and cyclooxygenase (thromboxane) metabolite receptors.

Conclusion

PASM cells produced LL-8 in response to LA, but not OA, under conditions of oxidative stress. The LL-8 response was mediated by AA metabolites.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology’, Virginia Commonwealth University Medical Center, P.O. Box 980034, Richmond, VA, 23298-0034, USA

    Courtney E. Leik PhD & Scott W. Walsh PhD

Authors
  1. Courtney E. Leik PhD
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  2. Scott W. Walsh PhD
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Corresponding author

Correspondence to Scott W. Walsh PhD.

Additional information

Supported by grants from the American Heart Association (AHA0051292U) and the National Institutes of Health (HL069851) to S.W.W.

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Leik, C.E., Walsh, S.W. Linoleic Acid, but not Oleic Acid, Upregulates Production of lnterleukin-8 by Human Vascular Smooth Muscle Cells via Arachidonic Acid Metabolites Under Conditions of Oxidative Stress. Reprod. Sci. 12, 593–598 (2005). https://doi.org/10.1016/j.jsgi.2005.09.004

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  • DOI: https://doi.org/10.1016/j.jsgi.2005.09.004

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