title: TLR2 stimulates ABCA1 expression via PKC-η and PLD2 pathway.
abstract: ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound protein that regulates cardiovascular disease including atherosclerosis by the efflux of excess cholesterol from cells and by suppression of inflammation. Using a mouse macrophage cell line Raw264.7, we studied the importance of toll-like receptor 2 (TLR2) on ABCA1 expression and the signaling pathway responsible for TLR2-mediated ABCA1 expression. Interestingly, our data demonstrated that treatment of macrophages with TLR2 agonist Pam(3)CSK(4) significantly increased ABCA1 mRNA and protein levels. We found that ABCA1 induction is myeloid differentiation primary response gene 88 (MyD88)-dependent as well as TLR2-dependent. ABCA1 induction upon Pam(3)CSK(4) is controlled by protein kinase C-η (PKC-η) and phospholipase D2 (PLD2). Furthermore, direct treatment of dioctanoyl phosphatidic acid (diC(8)PA) into cells also induced ABCA1 mRNA and protein indicating that PLD2-mediated PA involve in the TLR2-stimulated ABCA1 expression. Cumulatively, these results demonstrate for the first time that activation of PKC-η and PLD2 signaling pathway is an important mechanism for regulation of TLR2-induced ABCA1 expression.
authors.affiliation: Department of Biochemistry & Molecular Biology, Aging-Associated Vascular Disease Research Center, Republic of Korea.
authors.forename: Dae-Weon
authors.initials: DW
authors.lastname: Park
authors.forename: Hyung-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Ji Hyo
authors.initials: JH
authors.lastname: Lyu
authors.forename: Haemin
authors.initials: H
authors.lastname: Chin
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Young-Jo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.forename: Suk-Hwan
authors.initials: SH
authors.lastname: Baek
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002460:Cell Line; D055666:Lipopeptides / Q000494:pharmacology; D053858:Metabolic Networks and Pathways; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D055666:Lipopeptides; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; C508075:Pam(3)CSK(4) peptide; D034741:RNA, Small Interfering; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; C081975:protein kinase C eta; D011493:Protein Kinase C; C105606:phospholipase D2; D010739:Phospholipase D