Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1 beta.
There is good evidence that the n-3 polyunsaturated fatty acids (PUFAs) in fish oil have antiinflammatory effects and reduce the pathogenesis of atherosclerosis. However, the mechanisms underlying these actions are largely unknown. This study was designed to investigate the effects of membrane incorporation of two major components of fish oil [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], on rat smooth muscle cells (SMCs) activation induced by interleukin-1 beta (IL1 beta). We compared their effects with those of n-6 arachidonic acid (AA). Expression of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 adhesion molecules involved in SMCs migration was enhanced by AA, whereas EPA and DHA had no similar effects. We established that AA potentiates IL1 beta-induced expression of the type IIA secreted phospholipase A2 (sPLA2) gene, whereas EPA and DHA reduce this stimulation. EPA and DHA also abolished proinflammatory prostaglandin PGE2 production by inhibiting the IL1 beta-induced production of cyclooxygenase-2 (COX-2) mRNA. Much interest was then focused on three transcriptional factors implicated in inflammation control and especially in modulating rat sPLA2 and COX-2 gene transcription: nuclear factor-kappa B, CCAAT/enhancer binding protein beta, and E26 transformation-specific-1. electrophoretic mobility shift assay revealed that the binding activity of all three factors was increased by AA and reduced (or not affected) by n-3 PUFA. These results indicate that EPA and DHA act in opposition to AA by modulating various steps of the inflammatory process induced by IL1 beta, probably by reducing mitogen-activated protein kinase p42/p44 activity.
Bousserouel
Souad
S
UMR Physiologie et Physiopathologie, Université Pierre et Marie Curie, case courrier 256, Bâtiment A, 5éme étage, 7 quai Saint Bernard, 75252 Paris Cedex 5, France.
Brouillet
Arthur
A
Béréziat
Gilbert
G
Raymondjean
Michel
M
Andréani
Marise
M
D000818:Animals; D001011:Aorta; D018932:Chemokine CCL2 / Q000235:genetics; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D018932:Chemokine CCL2; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D007375:Interleukin-1; D007527:Isoenzymes; D010743:Phospholipids; D014157:Transcription Factors; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1; C077446:Pikasol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone