High-mobility Group Box-1 contribute to proinflammatory activation of macrophage on the acute spinal cord injury in rats

Keno Uchida
Department of Orthopaedics and Rehabilitation Medicine Faculty of Medical Sciences, University of Fukui Eiheiji, Fukui 910-1193, Japan

Abstract:

Objectives:
To elucidate the contribution of High-mobility group box-1(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.

Methods:
Injured thoracic spinal cord from adult 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.

Results:
HMGB-1 expression appeared earlier than that of tumor necrosis factor (TNF)-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 was confirmed at three days after injury.

Conclusion:
The release of HMGB-1 from neurons and macrophages is mediated through the HMGB-1/RAGE or TLR pathways. HMGB-1 plays a role in the proinflammatory cascade driving the secondary damage of spinal cord injury.