Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 390, Issue 2, Pages 196-200Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.09.009
Keywords
CpG ODN; TLR9; MyD88; Egr-1; Foam cell
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Funding
- Korean Science and Engineering Foundation via the Aging-associated Vascular Disease Research Center [R13-2005-005-02001-0, R01-2007-000-20087-0]
- National Research Foundation of Korea [R01-2007-000-20087-0, R13-2005-005-02001-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Early growth response-1 (Egr-1), a zinc finger transcription factor, plays a key regulatory role in pathological cardiovascular processes including atherosclerosis. Here, we investigate whether Egr-1 expression and foam cell formation require toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88). CpG DNA and its related synthetic CpG oligodeoxynucleotides (CpG ODN) play an important role in immunity and inflammation. CpG ODN increased expression of Egr-1 and formation of foam cells in Raw264.7 cells or bone marrow-derived macrophages. Egr-1 siRNA decreased foam cell formation by CpG ODN compared to that of control siRNA. In addition, when TLR9 or MyD88 was knocked down, CpG ODN-induced Egr-1 expression was also attenuated. CpG ODN increased ERK1/2 phosphorylation. U0126, a MEK pathway inhibitor, suppressed activation of Egr-1 expression by CpG ODN. CpG ODN-induced expression of tissue factor (TF) and NGFI-A binding protein 2 (Nab2), and the expression of both genes is blocked by knockdown of TLR9 or MyD88 siRNA or MEK inhibition. These results suggest that CpG ODN activates the TLR9-MyD88-ERK1/2 pathway causing expression of Egr-1 and its target genes such as TF and Nab2, thus inducing foam cell formation. (C) 2009 Elsevier Inc. All rights reserved.
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