Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid.

Bor-Ren Huang, Cheng-Fang Tsai, Hsiao-Yun Lin, Wen-Pei Tseng, Shiang-Suo Huang, Chi-Rei Wu, Chingju Lin, Wei-Lan Yeh, Dah-Yuu Lu

Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung, Taiwan.

Toxicology and applied pharmacology 2013 May 15

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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. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Bor-Ren Huang, Cheng-Fang Tsai, Hsiao-Yun Lin, Wen-Pei Tseng, Shiang-Suo Huang, Chi-Rei Wu, Chingju Lin, Wei-Lan Yeh, Dah-Yuu Lu. Interaction of inflammatory and anti-inflammatory responses in microglia by Staphylococcus aureus-derived lipoteichoic acid. Toxicology and applied pharmacology. 2013 May 15;269(1):43-50