Open AccessBacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-β Signaling Pathway
Author(s) -
Ju-Hyun Kim,
Seon-Ju Kim,
Im Soon Lee,
MyungShik Lee,
Satoshi Uematsu,
Shizuo Akira,
Kwon Ik Oh
Publication year - 2009
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.0801364
Subject(s) - hmgb1 , sepsis , signal transducing adaptor protein , mediator , signal transduction , high mobility group , stat , inflammation , receptor , jak stat signaling pathway , toll like receptor , biology , microbiology and biotechnology , immunology , innate immune system , immune system , stat3 , biochemistry , tyrosine kinase , gene
Sepsis is a devastating condition characterized by a systemic inflammatory response. Recently, high mobility group box 1 (HMGB1) was identified as a necessary and sufficient mediator of the lethal systemic inflammation caused by sepsis. However, despite its clinical importance, the mechanism of HMGB1 release has remained to be elusive. In this study, we demonstrate that the IFN-beta-mediated JAK/STAT pathway is essential for LPS or Escherichia coli-induced HMGB1 release, which is dependent on Toll/IL-1R domain-containing adapter-inducing IFN-beta adaptor. Additionally, we show that NO acts as a downstream molecule of the IFN-beta signaling. Furthermore, the JAK inhibitor treatment as well as the STAT-1 or IFN-beta receptor deficiency reduced HMGB1 release in a murine model of endotoxemia. Our results suggest that HMGB1 release in sepsis is dependent on the IFN-beta signaling axis; thus, therapeutic agents that selectively inhibit IFN-beta signaling could be beneficial in the treatment of sepsis.