PMID- 19737531 OWN - NLM STAT- MEDLINE DCOM- 20091130 LR - 20091026 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 390 IP - 2 DP - 2009 Dec 11 TI - Early growth response-1 is involved in foam cell formation and is upregulated by the TLR9-MyD88-ERK1/2 pathway. PG - 196-200 LID - 10.1016/j.bbrc.2009.09.009 [doi] AB - 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. FAU - Kim, Jin-Sik AU - Kim JS AD - Aging-Associated Vascular Disease Research Center, Department of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea. FAU - Park, Dae-Weon AU - Park DW FAU - Lee, Hyung-Kyoung AU - Lee HK FAU - Kim, Jae-Ryong AU - Kim JR FAU - Baek, Suk-Hwan AU - Baek SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090906 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (CPG-oligonucleotide) RN - 0 (Early Growth Response Protein 1) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Nab2 protein, mouse) RN - 0 (Neoplasm Proteins) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Repressor Proteins) RN - 0 (Toll-Like Receptor 9) RN - 9035-58-9 (Thromboplastin) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Cell Line MH - Early Growth Response Protein 1/genetics/*physiology MH - Foam Cells/metabolism/*physiology MH - Gene Expression Regulation MH - Mice MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Myeloid Differentiation Factor 88/metabolism MH - Neoplasm Proteins/genetics MH - Oligodeoxyribonucleotides/genetics MH - Repressor Proteins/genetics MH - Thromboplastin/genetics MH - Toll-Like Receptor 9/metabolism MH - Up-Regulation EDAT- 2009/09/10 06:00 MHDA- 2009/12/16 06:00 CRDT- 2009/09/10 06:00 PHST- 2009/08/28 00:00 [received] PHST- 2009/09/02 00:00 [accepted] PHST- 2009/09/10 06:00 [entrez] PHST- 2009/09/10 06:00 [pubmed] PHST- 2009/12/16 06:00 [medline] AID - S0006-291X(09)01786-0 [pii] AID - 10.1016/j.bbrc.2009.09.009 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2009 Dec 11;390(2):196-200. doi: 10.1016/j.bbrc.2009.09.009. Epub 2009 Sep 6.