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.
Vitis coignetiae Pulliat (Meoru in Korea) has been used as a remedy for inflammatory diseases and various cancers. We isolated anthocyanins from Meoru. We previously suggested that anthocyanins from fruits of Vitis coignetiae Pulliat (Meoru in Korea) should have anti-invasive effects through suppression of NF-κB activation. Here, we investigated their effects on NF-κB-regulated gene products and cellular responses in human lung cancer cells. The anthocyanins inhibited NF-κB activation in a dose-dependent manner. TNF-α augmented proliferation, migration and invasion of A549 cells. The anthocyanins inhibited the augmented proliferation, migration and invasion of the cancer cells by TNF-α. We also found that the anthocyanins suppressed NF-κB-regulated proteins involved in caner proliferation, metastasis and anti-apoptosis. The anthocyanins inhibit NF-κB activity by inhibiting IκBα phosphorylation. Taken together, this study suggested that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit the NF-κB activation and downstream proteins, which may be a factor in their anticancer activities of fruit of Vitis coignetiae Pulliat. Keywords: anthocyanins, Vitis coignetiae Pulliat, NF-κB, cancer * This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (0820050) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4451.
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