Sickle cell disease increases high mobility group box 1: a novel mechanism of inflammation.
Publication/Presentation Date
12-18-2014
Abstract
High mobility group box 1 (HMGB1) is a chromatin-binding protein that maintains DNA structure. On cellular activation or injury, HMGB1 is released from activated immune cells or necrotic tissues and acts as a damage-associated molecular pattern to activate Toll-like receptor 4 (TLR4). Little is known concerning HMGB1 release and TLR4 activity and their role in the pathology of inflammation of sickle cell disease (SCD). Circulating HMGB1 levels were increased in both humans and mice with SCD compared with controls. Furthermore, sickle plasma increased HMGB1-dependent TLR4 activity compared with control plasma. HMGB1 levels were further increased during acute sickling events (vasoocclusive crises in humans or hypoxia/reoxygenation injury in mice). Anti-HMGB1 neutralizing antibodies reduced the majority of sickle plasma-induced TLR4 activity both in vitro and in vivo. These findings show that HMGB1 is the major TLR4 ligand in SCD and likely plays a critical role in SCD-mediated inflammation.
Volume
124
Issue
26
First Page
3978
Last Page
3981
ISSN
1528-0020
Published In/Presented At
Xu, H., Wandersee, N. J., Guo, Y., Jones, D. W., Holzhauer, S. L., Hanson, M. S., Machogu, E., Brousseau, D. C., Hogg, N., Densmore, J. C., Kaul, S., Hillery, C. A., & Pritchard, K. A., Jr (2014). Sickle cell disease increases high mobility group box 1: a novel mechanism of inflammation. Blood, 124(26), 3978–3981. https://doi.org/10.1182/blood-2014-04-560813
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
25339362
Department(s)
Administration and Leadership
Document Type
Article