National Changhua University of Education Institutional Repository : Item 987654321/17858
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题名: Interaction of Inflammatory and Anti-inflammatory Responses in Microglia by Staphylococcus Aureus-derived Lipoteichoic Acid
作者: Huang, Bor-Ren;Tsai, Cheng-Fang;Lin, Hsiao-Yun;Tseng, Wen-Pei;Huang, Shiang-Suo;Wu, Chi-Rei;Lin, Chingju;Yeh, Wei-Lan;Lu, Dah-Yuu
贡献者: 運動健康所
关键词: Lipoteichoic acid;Microglia;Inflammation;Anti-inflammation;HO-1
日期: 2013-05
上传时间: 2014-01-15T04:02:54Z
出版者: Elsevier
摘要: We investigated the interaction between proinflammatory and inflammatory responses caused by Staphylococcus aureus-derived lipoteichoic acid (LTA) in primary cultured microglial cells and BV-2 microglia. LTA induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels increase in a concentration- and time-dependent manner. Meanwhile, LTA also increased nitric oxide (NO) and PGE2 production in microglia. Administration of TLR2 antagonist effectively inhibited LTA-induced NO, iNOS, and COX-2 expression. Moreover, treatment of cells with LTA caused a time-dependent activation of ERK, p38, JNK, as well as AKT. We also found that LTA-induced iNOS and COX-2 up-regulation were attenuated by p38, JNK, and PI3-kinase inhibitors. On the other hand, LTA-enhanced HO-1 expression was attenuated by p38 and PI3-kinase inhibitors. Treatment of cells with NF-κB and AP-1 inhibitors antagonized LTA-induced iNOS and COX-2 expression. However, only NF-κB inhibitors reduced LTA-induced HO-1 expression in microglia. Furthermore, stimulation of cells with LTA also activated IκBα phosphorylation, p65 phosphorylation at Ser536, and c-Jun phosphorylation. Moreover, LTA-induced increases of κB-DNA and AP-1-DNA binding activity were inhibited by p38, JNK, and PI3-kinase inhibitors. HO-1 activator CoPP IX dramatically reversed LTA-induced iNOS expression. Our results provided mechanisms linking LTA and inflammation/anti-inflammation, and indicated that LTA plays a regulatory role in microglia activation.
關聯: Toxicology and Applied Pharmacology, 269(1): 43-50
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