High-Mobility Group Box-1 and Its Receptors Contribute to Proinflammatory Response in the Acute Phase of Spinal Cord Injury in Rats

To examine the localization and expression of high-mobility group box-1 (HMGB-1) protein and its receptors after rat spinal cord injury. To elucidate the contribution of HMGB-1 and its receptors as potential candidates in a specific upstream pathway to the proinflammatory response leading to a casca...

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Bibliographic Details
Published in:Spine (Philadelphia, Pa. 1976) Pa. 1976), 2011-12, Vol.36 (25), p.2122-2129
Main Authors: CHEN, Ke-Bing, UCHIDA, Kenzo, BABA, Hisatoshi, NAKAJIMA, Hideaki, YAYAMA, Takafumi, HIRAI, Takayuki, RODRIGUEZ GUERRERO, Alexander, KOBAYASHI, Shigeru, MA, Wei-Ying, LIU, Shao-Yu, PING ZHU
Format: Article
Language:English
Subjects:
Acute-Phase Reaction - etiology
Acute-Phase Reaction - metabolism
Animals
Anterior Horn Cells - metabolism
Anterior Horn Cells - ultrastructure
Biological and medical sciences
Cerebrospinal fluid. Meninges. Spinal cord
Cytokines - metabolism
Fluorescent Antibody Technique
HMGB1 Protein - metabolism
Immunoblotting
Immunohistochemistry
Inflammation Mediators - metabolism
Injuries of the nervous system and the skull. Diseases due to physical agents
Interleukin-1 - metabolism
Interleukin-6 - metabolism
Macrophages - metabolism
Medical sciences
Microscopy, Immunoelectron
Nervous system (semeiology, syndromes)
Neurology
Neurons - metabolism
Protein Binding
Rats
Receptor for Advanced Glycation End Products
Receptors, Immunologic - metabolism
Spinal Cord Injuries - complications
Spinal Cord Injuries - metabolism
Time Factors
Toll-Like Receptor 2 - metabolism
Toll-Like Receptor 4 - metabolism
Traumas. Diseases due to physical agents
Tumor Necrosis Factor-alpha - metabolism
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Summary:To examine the localization and expression of high-mobility group box-1 (HMGB-1) protein and its receptors after rat spinal cord injury. To elucidate the contribution of HMGB-1 and its receptors as potential candidates in a specific upstream pathway to the proinflammatory response leading to a cascade of secondary tissue damage after spinal cord injury. HMGB-1 was recently characterized as a key cytokine with a potential role in nucleosome formation and regulation of gene transcription. No studies have investigated the role of HMGB-1 in spinal cord injury. Injured thoracic spinal cord from 62 rats aged 8 to 12 weeks and spinal cord from 20 control rats were examined. HMGB-1 was localized by immunofluorescence staining, costaining with cell markers, and by immunoelectron microscopy. The expression of HMGB-1 and its receptors, receptor for advanced glycation end products (RAGE), toll-like receptor (TLR)2, and TLR4 were also examined by immunohistochemistry. HMGB-1 expression appeared earlier than that of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in the spinal cord injury rats, with the HMGB-1 produced by both macrophages and neurons. HMGB-1 translocated from nucleus to cytoplasm in some neurons at an early stage after neural injury. Increased expression of HMGB-1, RAGE, and TLRs was observed after injury, and interaction of HMGB-1 with RAGE or TLRs, particularly in macrophage, was confirmed at 3 days after injury. Our results demonstrated an earlier onset in the expression of HMGB-1 than in tumor necrosis factor-α, IL-1β, and IL-6 after spinal cord injury. The release of HMGB-1 from neurons and macrophages is mediated through the HMGB-1/RAGE or TLR pathways. HMGB-1 seems to play at least some roles in the proinflammatory cascade originating the secondary damage after the initial spinal cord injury.
ISSN:0362-2436
1528-1159
DOI:10.1097/brs.0b013e318203941c