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  • Title: Lipoteichoic acid of Staphylococcus aureus enhances IL-6 expression in activated human basophils.
    Author: Jeon JH, Kim SK, Baik JE, Kang SS, Yun CH, Chung DK, Han SH.
    Journal: Comp Immunol Microbiol Infect Dis; 2012 Jul; 35(4):363-74. PubMed ID: 22445541.
    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.
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