title: TNFa alter cholesterol metabolism in human macrophages via PKC-θ-dependent pathway.
abstract: BACKGROUND
  Studies have shown that inflammation promoted atherosclerotic progression; however, it remains unclear whether inflammation promoted atherosclerotic progression properties by altering cholesterol metabolism in human macrophages. In the present study, we evaluated a potential mechanism of inflammation on atherogenic effects. We evaluated the ability of TNFa to affect Reverse cholesterol transport (RCT) and cholesterol uptake and its mechanism(s) of action in human macrophages.
  
  
  RESULTS
  We initially determined the potential effects of TNFa on cholesterol efflux in the human macrophages. We also determined alterations in mRNA and protein levels of ABCA1, ABCG1, LXRa, CD-36, SR-A in human macrophages using quantitative real-time polymerase chain reaction (PCR) and Western immunoblot analyses. The cholesterol efflux rate and protein expression of ABCA1, ABCG1, LXRa, CD-36, SR-A were quantified in human macrophages under PKC-θ inhibition using PKC-θ siRNA. Our results showed that TNFa inhibited the rate of cholesterol efflux and down-regulation the expression levels of ABCA1, ABCG1 and LXRa and up-regulation the expression levels of CD-36, SR-A in human macrophages; PKC-θ inhibition by PKC-θ siRNA attenuated the effect of TNFa on ABCA1, ABCG1, LXRa, SR-A, CD-36 expression.
  
  
  CONCLUSIONS
  Our results suggest TNFa alter cholesterol metabolism in human macrophages through the inhibition of Reverse cholesterol transport and enhancing cholesterol uptake via PKC-θ-dependent pathway, implicating a potential mechanism of inflammation on atherogenic effects.
authors.affiliation: Department of Cardiology, Southwest Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: A Zhi Sha
authors.initials: AZ
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhi Yuan
authors.initials: ZY
authors.lastname: Song
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D007527:Isoenzymes; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta
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