title: Lipoteichoic acid of Staphylococcus aureus enhances IL-6 expression in activated human basophils.
abstract: At allergic inflammation, cross-linking of FcɛRI with multivalent antigen-bound IgE triggers the signaling pathways via activation of protein kinase C (PKC) and mobilization of intracellular Ca(2+) leading to the production of various mediators such as interleukin-6 (IL-6). Accumulating reports demonstrated that interaction of Toll-like receptor 2 (TLR2) expressed on basophils with a TLR2 ligand, lipoteichoic acid (LTA) of Staphylococcus aureus, exacerbated allergic inflammation. Here, we showed that staphylococcal LTA (Sa.LTA) substantially enhanced IL-6 expression at both the protein and the mRNA levels in the human basophil line, KU812, in the presence of a PKC activator (phorbol 12-myristrate 13-acetate; PMA), and a calcium ionophore (A23187), whereas Sa.LTA alone could not induce IL-6 expression. PMA/A23187 augmented the expression of CD14 and TLR2 on the surface of KU812 cells and concomitantly increased the binding of fluorochrome-labeled Sa.LTA to the cells. Sa.LTA enhanced the phosphorylation of mitogen-activated protein (MAP) kinases in PMA/A23187-stimulated KU812 cells. Notably, Sa.LTA could not enhance PMA/A23187-induced IL-6 expression in the presence of inhibitors of MAP kinases, reactive oxygen species, or protein kinase C. Furthermore, Sa.LTA enhanced the PMA/A23187-increased DNA-binding activities of the transcription factors NF-κB and AP-1. Experiments using human peripheral blood mononuclear cells demonstrated that not only PMA/A23187 but also Sa.LTA increased the intracellular IL-6 expression in the basophil population and Sa.LTA plus PMA/A23187 further enhanced the IL-6 expression. Collectively, these results suggest that Sa.LTA exacerbates allergic inflammation by potentiating IL-6 production from activated basophils.
authors.affiliation: Department of Agricultural Biotechnology, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jeon
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Baik
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002460:Cell Line; D004357:Drug Synergism; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000276:immunology; D013682:Teichoic Acids / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology
chemical_list: D061207:Calcium Ionophores; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D018808:Transcription Factor AP-1; D000001:Calcimycin; C009900:lipoteichoic acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate