Linoleic acid, but not oleic acid, upregulates production of interleukin-8 by human vascular smooth muscle cells via arachidonic acid metabolites under conditions of oxidative stress.
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 IL-8, prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) production. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated gene expression in PASM cells for representative lipoxygenase (LTB4) and cyclooxygenase (thromboxane) metabolite receptors.


CONCLUSIONS
PASM cells produced IL-8 in response to LA, but not OA, under conditions of oxidative stress. The IL-8 response was mediated by AA metabolites.
Leik
Courtney E
CE
Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0034, USA.
Walsh
Scott W
SW
D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000235:genetics / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology*; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D016209:Interleukin-8; D007975:Leukotriene B4; D016718:Arachidonic Acid; D019301:Oleic Acid; D013929:Thromboxane B2; D019787:Linoleic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases