Document Detail


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.
MedLine Citation:
PMID:  16325749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. CONCLUSION: 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.
Authors:
Courtney E Leik; Scott W Walsh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the Society for Gynecologic Investigation     Volume:  12     ISSN:  1556-7117     ISO Abbreviation:  J. Soc. Gynecol. Investig.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-04-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9433806     Medline TA:  J Soc Gynecol Investig     Country:  United States    
Other Details:
Languages:  eng     Pagination:  593-8     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0034, USA.
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acid / metabolism*
Cells, Cultured
Female
Gene Expression
Humans
Interleukin-8 / biosynthesis*
Leukotriene B4 / genetics,  metabolism
Linoleic Acid / pharmacology*
Lipoxygenase / metabolism
Muscle, Smooth, Vascular / cytology,  drug effects,  metabolism*
Oleic Acid / pharmacology*
Oxidative Stress / physiology*
Pre-Eclampsia / metabolism
Pregnancy
Prostaglandin-Endoperoxide Synthases / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Thromboxane B2 / genetics,  metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL069851/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-8; 112-80-1/Oleic Acid; 2197-37-7/Linoleic Acid; 506-32-1/Arachidonic Acid; 54397-85-2/Thromboxane B2; 71160-24-2/Leukotriene B4; EC 1.13.11.12/Lipoxygenase; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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