title: Inhibition of arthritis in the Lewis rat by apolipoprotein A-I and reconstituted high-density lipoproteins.
abstract: OBJECTIVE
  This study questions whether high-density lipoproteins (HDLs) and apolipoprotein A-I inhibit joint inflammation in streptococcal cell wall peptidoglycan-polysaccharide (PG-PS)-induced arthritis in female Lewis rats.
  
  
  RESULTS
  Administration of PG-PS to female Lewis rats caused acute joint inflammation after 4 days, followed by remission by day 8. The animals subsequently developed chronic joint inflammation that persisted until euthanasia at day 21. Treatment with apolipoprotein A-I 24 hours before and 24 hours after PG-PS administration reduced the acute and chronic joint inflammation. Treatment with apolipoprotein A-I at days 7, 9, and 11 after PG-PS administration reduced the chronic joint inflammation. Treatment with apolipoprotein A-I or reconstituted HDLs consisting of apolipoprotein A-I complexed with phosphatidylcholine 24 hours before and at days 1, 7, 9, and 11 after PG-PS administration reduced acute and chronic joint inflammation. Treatment with apolipoprotein A-I also reduced the inflammatory white blood cell count, synovial fluid proinflammatory cytokine levels, synovial tissue macrophage accumulation, as well as toll-like receptor 2, and inflammatory cytokine expression. At the molecular level, preincubation of human monocyte-derived macrophages with apolipoprotein A-I or reconstituted HDLs before PG-PS stimulation inhibited the PG-PS-induced increase in toll-like receptor 2 and myeloid differentiation primary response gene (88) mRNA levels, nuclear factor-κB activation, and proinflammatory cytokine production. The effects of apolipoprotein A-I and reconstituted HDLs were abolished by transfecting the human monocyte-derived macrophages with ATP-binding cassette transporter A1 or G1 siRNA.
  
  
  CONCLUSIONS
  Apolipoprotein A-I and reconstituted HDLs attenuate PG-PS-induced arthritis in the rat. Studies in human monocyte-derived macrophages indicate that this benefit may be because of the inhibition of toll-like receptor 2 expression and decreased nuclear factor-κB activation in macrophages.
authors.affiliation: From the Lipid Research Group, The Heart Research Institute, Sydney, New South Wales, Australia (B.J.W., K.L.O., S.S., K.C., F.T., P.J.B., K.-A.R.); Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia (B.J.W., K.L.O., F.T., P.J.B., K.-A.R.); and Centre for Vascular Research, The University of New South Wales, Sydney, New South Wales, Australia (B.J.W., K.L.O., S.S., F.T., P.J.B., K.-A.R.).
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Wu
authors.forename: Kwok L
authors.initials: KL
authors.lastname: Ong
authors.forename: Sudichhya
authors.initials: S
authors.lastname: Shrestha
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Fatiha
authors.initials: F
authors.lastname: Tabet
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D008076:Cholesterol, HDL / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008075:Lipoproteins, HDL / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000378:metabolism; D022423:Myeloid Cells / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010457:Peptidoglycan / Q000633:toxicity; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011135:Polysaccharides, Bacterial / Q000633:toxicity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D016207:Cytokines; D008075:Lipoproteins, HDL; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010457:Peptidoglycan; D010713:Phosphatidylcholines; D011135:Polysaccharides, Bacterial; D034741:RNA, Small Interfering; D051195:Toll-Like Receptor 2; C577836:ABCA1 protein, human; C577834:Abca1 protein, rat; C519043:CSL-111; C507781:Myd88 protein, rat; C495343:Tlr2 protein, rat; C037978:high density lipoprotein phosphatidylcholine
keywords: apolipoprotein A-I; arthritis, rheumatoid; cholesterol, HDL; inflammation