HMGB1 Binds to Lipoteichoic Acid and Enhances TNF-alpha and IL-6 Production through HMGB1-Mediated Transfer of Lipoteichoic Acid to CD14 and TLR2

作者：Kwak Man Sup; Lim Mihwa; Lee Yong Joon; Lee Hyun Sook; Kim Young Hun; Youn Ju Ho; Choi Ji Eun; Shin Jeon Soo^*

来源：Journal of Innate Immunity, 2015, 7(4): 405-416.

DOI：10.1159/000369972

• HMGB1
• Gram-positive bacteria
• Lipoteichoic acid
• TLR2
• Inflammation

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-kappa B p65 nuclear transmigration, degradation of I kappa B alpha and reporter assay results demonstrated that NF-kappa B 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-alpha 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.

• 出版日期2015