HMGB1 Activates Proinflammatory Signaling via TLR5 Leading to Allodynia

被引:127
作者
Das, Nabanita [1 ,2 ]
Dewan, Varun [1 ,2 ]
Grace, Peter M. [3 ,4 ]
Gunn, Robin J. [5 ]
Tamura, Ryo [1 ,2 ]
Tzarum, Netanel [5 ]
Watkins, Linda R. [3 ,4 ]
Wilson, Ian A. [5 ,6 ]
Yin, Hang [1 ,2 ]
机构
[1] Univ Colorado, Dept Chem & Biochem, Campus Box 215, Boulder, CO 80309 USA
[2] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA
[3] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA
[4] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA
[5] Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA
[6] Scripps Res Inst, Skaggs Inst Chem Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA
关键词
TOLL-LIKE RECEPTORS; GLYCATION END-PRODUCTS; MECHANICAL ALLODYNIA; BACTERIAL FLAGELLIN; CHROMATIN PROTEIN; NERVOUS-SYSTEM; IMMUNE; INFLAMMATION; BINDING; PAIN;
D O I
10.1016/j.celrep.2016.09.076
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation endproducts) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-kappa B signaling pathway in a MyD88-dependent manner, resulting in proinflammatory cytokine production and pain enhancement in vivo. Biophysical and in vitro results highlight an essential role for the C-terminal tail region of HMGB1 in facilitating interactions with TLR5. These results suggest that HMGB1-modulated TLR5 signaling is responsible for pain hypersensitivity.
引用
收藏
页码:1128 / 1140
页数:13
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