The Role of HMGB1/DAMPs on Structural Lung Abnormalities and Systemic Inflammation in Bronchiectasis

  • Lin, Horng-Chyuan (PI)
  • Kuo, Han-Ping (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Bronchiectasis is a chronic respiratory disease characterized by irreversibly dilated, thick-walled bronchi that are inflamed and colonized by bacteria. Patients may develop progressive decline in pulmonary function due to ongoing infection, inflammation, and destruction of bronchi if a delay in diagnosis and therapy occurs. Clinically, high-resolution computed tomography (HRCT) may add important information for outcome prediction, as it was proven to be more sensitive to detect and monitor bronchiectasis than pulmonary function tests. The patient’s clinical outcome may be impacted by the type of structural lung abnormality observed on HRCT. Moreover, bronchiectasis is a chronic, progressive lung disease with ongoing, airway and systemic inflammatory process encompassing recurrent infection, progressive lung damage and structural changes. Therefore, it raises the possibility that modulation of systemic inflammation could improve outcomes in bronchiectasis. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein, released actively following cytokine stimulation. It is the prototypic damage-associated molecular patterns (DAMPs) molecule and has been implicated in several inflammatory disorders. Previous studies had been demonstrated that HMGB1/DAMPs are involved in chronic inflammatory airway diseases: such as COPD, obstructive sleep apnea syndrome (OSAS), and cystic fibrosis, etc. Based on these findings, it is supposed that HMGB1/DAMPs and NF-B signaling pathways might involve in the airway and systemic inflammation, as well as the subsequently structural abnormalities in bronchiectasis. Future advances in this field will stem from understanding the biological basis for the success of targeting HMGB1 to therapeutic improvement in the treatment of bronchiectasis. Bronchiectasis remains a major cause of excess respiratory morbidity and treatment is generally only partly successful. There is an urgent need for improved anti-inflammatory therapy to treat bronchiectasis. Our study will give more clues about the mechanisms by which the therapies (anti-inflammatory therapy and pulmonary rehabilitation) on the NF-B/NRF and HMGB1/DAMPs pathways and inflammation (either pulmonary or systemic) in patients with bronchiectasis. Thus, our results may not only shed light on the mechanisms, either HMGB1/DAMPs regulation or inflammatory modulation, underlying the structural lung abnormalities in bronciectasis, but also provide a new therapeutic direction.

Project IDs

Project ID:PC10007-1146
External Project ID:NSC100-2314-B182A-086-MY3
Effective start/end date01/08/1131/07/12


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