Observation of inflammation and macrophage polarization in an experimental model of cigarette smoke-exposed mice and cigarette smoke extract (CSE)-induced RAW264.7 cells: An experimental preclinical study.

Authors

Jiazhen Zhao, Yang Liu, Yaxi Li, Zhiyuan Liu, Min Tan, Changhui Wang, Xuan Long, Xiaolian Song

Published in

Tobacco induced diseases. Volume 24. Epub Jul 26, 2026.

Abstract

The present study aimed to investigate macrophage polarization imbalance and its association with sustained NF-κB/NLRP3 signaling under chronic inflammatory stimulation using both in vivo and in vitro COPD-related models.
This experimental preclinical study was conducted between March and September 2023, at Shanghai Tenth People's Hospital. A chronic obstructive pulmonary disease (COPD)-like inflammatory model was established in C57BL/6J mice (n=5 per group) through combined chronic cigarette smoke (CS) exposure (4 hours/day, 5 days/week for 15 weeks) and intranasal lipopolysaccharide (LPS) administration (7.5 μg on days 1 and 14), together with an in vitro cigarette smoke extract (CSE)-induced RAW264.7 macrophage model (10% CSE for 24 hours). Macrophage M1/M2 polarization and inflammatory responses were assessed using ELISA, qRT-PCR, immunohistochemistry, Western blotting, and flow cytometry.
Airflow limitation was observed in CS-exposed model mice, with significant reductions in FEV_0.05/FVC (21.70 ± 0.96 vs 27.50 ± 0.94%, p<0.0001) and FEV_0.1/FVC (77.39 ± 2.62 vs 87.21 ± 1.95%, p<0.001), along with increased lung resistance (RL: 1.22 ± 0.13 vs 0.97 ± 0.02 cmH₂O/(mL/s), p<0.01). Histological examination revealed thickened bronchial walls, disrupted alveolar structure, and inflammatory cell infiltration. TNF-α (BALF: 290.6 ± 7.58 vs 125.6 ± 5.30 pg/mL, p<0.0001), IL-6 (BALF: 67.92 ± 3.02 vs 44.42 ± 2.62 pg/mL, p<0.001), and IL-1β (BALF: 120.3 ± 8.24 vs 87.52 ± 3.40 pg/mL, p<0.01) levels increased dramatically in both CS-exposed mice and CSE-induced RAW264.7 cells, whereas IL-10 levels decreased (BALF: 46.12 ± 1.71 vs 77.19 ± 3.96 pg/mL, p<0.001).
CS and CSE exposure induced M1 macrophage polarization in mice, as well as 10% CSE-induced RAW 264.7 cells, which may be related to the activation of the NF-κB/NLRP3 signaling pathway.

PMID:
42529710
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

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