연구성과 홍보

J Inflamm (Lond). 2024 Apr 24;21(1):13.

Title : Fine particulate matter aggravates smoking induced lung injury via NLRP3/caspase-1 pathway in COPD

Authors : Chiwook Chung^#1,2, Suk Young Park#1, Jin-Young Huh1,3, Na Hyun Kim1, ChangHo Shon1,4, Eun Yi Oh1,5, Young-Jun Park6, Seon-Jin Lee6, Hwan-Cheol Kim7, Sei Won Lee8*

Affiliations :

1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea.

2Department of Pulmonary and Critical Care Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea.

3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chung- Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Republic of Korea.

4Efficacy Evaluation Center, WOOJUNGBIO Inc, Hwaseong, Republic of Korea.

5Department of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.

6Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.

7Department of Occupational and Environmental Medicine, College of Medicine, Inha University, Incheon, Republic of Korea.

8Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505, Seoul, Republic of Korea.

DOI: 10.1186/s12950-024-00384-z.

Abstract :

Background: Exposure to noxious particles, including cigarette smoke and fine particulate matter (PM2.5), is a risk factor for chronic obstructive pulmonary disease (COPD) and promotes inflammation and cell death in the lungs. We investigated the combined effects of cigarette smoking and PM2.5 exposure in patients with COPD, mice, and human bronchial epithelial cells.

Methods: The relationship between PM2.5 exposure and clinical parameters was investigated in patients with COPD based on smoking status. Alveolar destruction, inflammatory cell infiltration, and pro-inflammatory cytokines were monitored in the smoking-exposed emphysema mouse model. To investigate the mechanisms, cell viability and death and pyroptosis-related changes in BEAS-2B cells were assessed following the exposure to cigarette smoke extract (CSE) and PM2.5.

Results: High levels of ambient PM2.5 were more strongly associated with high Saint George's respiratory questionnaire specific for COPD (SGRQ-C) scores in currently smoking patients with COPD. Combined exposure to cigarette smoke and PM2.5 increased mean linear intercept and TUNEL-positive cells in lung tissue, which was associated with increased inflammatory cell infiltration and inflammatory cytokine release in mice. Exposure to a combination of CSE and PM2.5 reduced cell viability and upregulated NLRP3, caspase-1, IL-1β, and IL-18 transcription in BEAS-2B cells. NLRP3 silencing with siRNA reduced pyroptosis and restored cell viability.

Conclusions: PM2.5 aggravates smoking-induced airway inflammation and cell death via pyroptosis. Clinically, PM2.5 deteriorates quality of life and may worsen prognosis in currently smoking patients with COPD.