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- Title
HMGB1 Binds to Lipoteichoic Acid and Enhances TNF-α and IL-6 Production through HMGB1-Mediated Transfer of Lipoteichoic Acid to CD14 and TLR2.
- Authors
Kwak, Man Sup; Lim, Mihwa; Lee, Yong Joon; Lee, Hyun Sook; Kim, Young Hun; Youn, Ju Ho; Choi, Ji Eun; Shin, Jeon-Soo
- Abstract
Lipoteichoic acid (LTA) is a component of the cell wall of Gram-positive bacteria and induces a toll-like receptor 2 (TLR2)-mediated inflammatory response upon initial binding to lipopolysaccharide-binding protein (LBP) and subsequent transfer to CD14. In this study, we identified a novel role for the nuclear protein high-mobility group box 1 (HMGB1) in LTA-mediated inflammation. Results of ELISA, surface plasmon resonance and native PAGE electrophoretic mobility shift analyses indicated that HMGB1 binds to LTA in a concentration-dependent manner and that this binding is inhibited by LBP. Native PAGE, fluorescence-based transfer and confocal imaging analyses indicated that HMGB1 catalytically disaggregates LTA and transfers LTA to CD14. NF-κB p65 nuclear transmigration, degradation of IκBα and reporter assay results demonstrated that NF-κB activity in HEK293-hTLR2/6 cells is significantly upregulated by a mixture of LTA and soluble CD14 in the presence of HMGB1. Furthermore, the production of TNF-α and IL-6 in J774A.1 and RAW264.7 cells increased significantly following treatment with a mixture of LTA and HMGB1 compared with treatment with LTA or HMGB1 alone. Thus, we propose that HMGB1 plays an important role in LTA-mediated inflammation by binding to and transferring LTA to CD14, which is subsequently transferred to TLR2 to induce an inflammatory response. © 2015 S. Karger AG, Basel
- Publication
Journal of Innate Immunity, 2015, Vol 7, Issue 4, p405
- ISSN
1662-811X
- Publication type
Article
- DOI
10.1159/000369972