TLR2 stimulates ABCA1 expression via PKC-eta and PLD2 pathway
- TLR2 stimulates ABCA1 expression via PKC-eta and PLD2 pathway
- 백석환; 박대원; 이형경; 류지효; 진해민[진해민]; 강상욱; 김영조; 배외식[배외식]
- FOAM CELL-FORMATION; CASSETTE TRANSPORTER A1; ATHEROSCLEROTIC LESION DEVELOPMENT; MACROPHAGE CHOLESTEROL EFFLUX; RECEPTOR KNOCKOUT MICE; TOLL-LIKE RECEPTORS; INFLAMMATORY RESPONSES; TOLL-LIKE-RECEPTOR-2; REGULATOR; DISEASE
- Issue Date
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.430, no.3, pp.933 - 937
- 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) CSK4 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 (PKC-eta) 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-eta and PLD2 signaling pathway is an important mechanism for regulation of TLR2-induced ABCA1 expression. (C) 2012 Elsevier Inc. All rights reserved.
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