title: Lipoteichoic acid of Enterococcus faecalis induces the expression of chemokines via TLR2 and PAFR signaling pathways.
abstract: Enterococcus faecalis is one of the most common opportunistic pathogens responsible for nosocomial infections, and its LTA is known as an important virulence factor causing inflammatory responses. As chemokines play a key role in inflammatory diseases by triggering leukocyte infiltration into the infection site, we purified EfLTA and investigated its effect on the expression of chemokines, IP-10, MIP-1α, and MCP-1, in murine macrophages. EfLTA induced the expression of these chemokines at the mRNA and protein levels. TLR2, CD14, and MyD88 were involved in the EfLTA-induced chemokine expression, as the expression was reduced remarkably in macrophages derived from TLR2-, CD14-, or MyD88-deficient mice. EfLTA induced phosphorylation of MAPKs and enhanced the DNA-binding activity of NF-κB, AP-1, and NF-IL6 transcription factors. The induction of IP-10 required ERK, JNK, p38 MAPK, PKC, PTK, PI3K, and ROS. We noticed that all of these signaling molecules, except p38 MAPK and ROS, were indispensable for the induction of MCP-1 and MIP-1α. Interestingly, the EfLTA-induced chemokine expression was mediated through PAFR/JAK/STAT1 signaling pathways without IFN-β involvement, which is different from LPS-induced chemokine expression requiring IFN-β/JAK/STAT1 signaling pathways. Furthermore, the culture supernatant of EfLTA-treated RAW 264.7 cells promoted the platelet aggregation, and exogenous PAF induced the chemokine expression in macrophages derived from WT and TLR2-deficient mice. These results suggest that EfLTA induces the expression of chemokines via signaling pathways requiring TLR2 and PAFR, which is distinct from that of LPS-induced chemokine expression.
authors: 1.DRI, and BK21 Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea. shhan-mi@snu.ac.kr.
authors: Ok-Jin
authors: OJ
authors: Park
authors: Ji Young
authors: JY
authors: Han
authors: Jung Eun
authors: JE
authors: Baik
authors: Jun Ho
authors: JH
authors: Jeon
authors: Seok-Seong
authors: SS
authors: Kang
authors: Cheol-Heui
authors: CH
authors: Yun
authors: Jong-Won
authors: JW
authors: Oh
authors: Ho Seong
authors: HS
authors: Seo
authors: Seung Hyun
authors: SH
authors: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D054405:Chemokine CCL3 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013293:Enterococcus faecalis / Q000737:chemistry* / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018345:Mice, Knockout; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C039351:platelet activating factor receptor; C009900:lipoteichoic acid; D016899:Interferon-beta; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: LTA; Platelet-activating factor; Toll-like receptor 2; macrophages