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

• Published in: Toxicology and applied pharmacology 2013-05, Vol.269 (1), p.43-50
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Anti-inflammation; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cells, Cultured; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; DNA; Dose-Response Relationship, Drug; Enzyme Activation; Heme Oxygenase (Decyclizing) - metabolism; HO-1; INFLAMMATION; Inflammation - immunology; Inflammation - metabolism; Inflammation - prevention & control; Inflammation Mediators - metabolism; Lipopolysaccharides - isolation & purification; Lipopolysaccharides - pharmacology; Lipoteichoic acid; Medical sciences; Microglia; Microglia - drug effects; Microglia - immunology; Microglia - metabolism; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NITRIC OXIDE; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Phosphatidylinositol 3-Kinase - antagonists & inhibitors; Phosphatidylinositol 3-Kinase - metabolism; PHOSPHORYLATION; Primary Cell Culture; Protein Kinase Inhibitors - pharmacology; PROTEINS; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; STAPHYLOCOCCUS; Staphylococcus aureus - metabolism; Teichoic Acids - isolation & purification; Teichoic Acids - pharmacology; TIME DEPENDENCE; Time Factors; Toll-Like Receptor 2 - antagonists & inhibitors; Toll-Like Receptor 2 - metabolism; Toxicology; Transcription Factor AP-1 - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2013.03.004

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. •LTA causes an increase in iNOS, COX-2, and HO-1 expression in microglia.•LTA induces iNOS and COX-2 expression through TLR-2/NF-κB and AP-1 pathways.•HO-1 expression is regulated through p38, JNK, PI3K/AKT and AP-1 pathways.•Induced HO-1 reduces LTA-induced iNOS expression.•LTA plays a regulatory role on inflammatory/anti-inflammatory responses.