In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation.
Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MPhi). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFalpha, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MPhi scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA- and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA- and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MPhi which are not related to the n position of the first double bond, chain length or degree of saturation.
Wang
Shu
S
JM USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Wu
Dayong
D
Lamon-Fava
Stefania
S
Matthan
Nirupa R
NR
Honda
Kaori L
KL
Lichtenstein
Alice H
AH
D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000494:pharmacology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis; D002784:Cholesterol / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000032:analysis; D019787:Linoleic Acid / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019814:Myristic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019814:Myristic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019308:Palmitic Acid; D002784:Cholesterol; D019787:Linoleic Acid