The HMGB1-RAGE Inflammatory Pathway: Implications for Brain Injury-Induced Pulmonary Dysfunction

Daniel J. Weber, Yohance M. Allette, David S. Wilkes, Fletcher A. White

Research output: Contribution to journalReview articlepeer-review

59 Scopus citations


Deceased patients who have suffered severe traumatic brain injury (TBI) are the largest source of organs for lung transplantation. However, due to severely compromised pulmonary lung function, only onethird of these patients are eligible organ donors, with far fewer capable of donating lungs (∼20%). As a result of this organ scarcity, understanding and controlling the pulmonary pathophysiology of potential donors are key to improving the health and long-term success of transplanted lungs. Recent Advances: Although the exact mechanism by which TBI produces pulmonary pathophysiology remains unclear, it may be related to the release of damage-associated molecular patterns (DAMPs) from the injured tissue. These heterogeneous, endogenous host molecules can be rapidly released from damaged or dying cells and mediate sterile inflammation following trauma. In this review, we highlight the interaction of the DAMP, high-mobility group box protein 1 (HMGB1) with the receptor for advanced glycation end-products (RAGE), and toll-like receptor 4 (TLR4). Critical Issues: Recently published studies are reviewed, implicating the release of HMGB1 as producing marked changes in pulmonary inflammation and physiology following trauma, followed by an overview of the experimental evidence demonstrating the benefits of blocking the HMGB1-RAGE axis. Future Directions: Targeting the HMGB1 signaling axis may increase the number of lungs available for transplantation and improve long-term benefits for organ recipient patient outcomes.

Original languageEnglish (US)
Pages (from-to)1316-1328
Number of pages13
JournalAntioxidants and Redox Signaling
Issue number17
StatePublished - Dec 10 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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