期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 94, 期 6, 页码 1275-1284出版社
OXFORD UNIV PRESS
DOI: 10.1189/jlb.1012522
关键词
macrophages; LTA; Toll-like receptor 2; Platelet-activating factor
资金
- National Research Foundation of Korea (NRF)
- Korean government [Ministry of Science, Information and Communications Technology and Future Planning (MSIP)] [2012-0008693, 2008-0062614, 2012-0007883]
- R&D Convergence Center Support Program, the Ministry for Food, Agriculture, Forestry and Fisheries (Republic of Korea)
- National Research Council of Science & Technology (NST), Republic of Korea [527730-13] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2008-0062614] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
E. faecalis lipoteichoic acid induces chemokine expression via TLR2/CD14/MyD88 and PAFR/JAK/STAT1 signaling pathways, without induction of IFN- in murine macrophages. 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-1, 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-B, 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-1. Interestingly, the EfLTA-induced chemokine expression was mediated through PAFR/JAK/STAT1 signaling pathways without IFN- involvement, which is different from LPS-induced chemokine expression requiring IFN-/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.
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