Article

Abstract

• 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-κB 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.

Creator

• Das, Nabanita
• Yin, Hang
• Wilson, Ian A
• Tzarum, Netanel
• Grace, Peter M
• Watkins, Linda R
• Gunn, Robin J
• Dewan, Varun
• Tamura, Ryo

Date Issued

• 2016-10-18

Academic Affiliation

• Psychology and Neuroscience

Journal Title

• Cell Reports

Journal Issue/Number

• 4

Journal Volume

• 17

File Extent

• 1128-1140

Subject

• Hyperalgesia
• NF-kappa B
• Signal Transduction
• Inflammation
• Cytokines
• Binding Sites
• HMGB1 Protein
• Rats
• Male
• Jurkat Cells
• HEK293 Cells
• Humans
• Toll-Like Receptor 5
• RAW 264.7 Cells
• Nitric Oxide
• Protein Binding
• Sprague-Dawley
• Mice
• Animals
• Amino Acid Sequence

Last Modified

• 2019-12-05

Identifier

• PubMed ID: 27760316

Resource Type

• Article

Rights Statement

• In Copyright

DOI

•  https://doi.org/10.1016/j.celrep.2016.09.076

ISSN

• 2211-1247

Language

• English [eng]

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