Cigarette smoke (CS)-exposed wild-type mice treated with an intraperitoneal injection (i.p) of mitoTEMPO (MT) reveal decreased productions of nuclear factor kappa B (NF-κB)-dependent inflammatory cytokines, but not type-I interferons (IFNs), alleviated airway inflammation, infiltration of neutrophil extracellular traps (NETs), and improved lung functions, as compared with CS-treated saline i.p mice. Statistical analysis: n = 7–16 for each bar in (b–l, n, p), data were presented as the mean ± standard deviation; Differences are assessed by the (b–l, n, p) two-way ANOVA analysis of variance, followed Tukey’s honest significant test; P < 0.05 represents a significant difference, the scattered samples and the p values are displayed in figures. a A brief outline for the experiments of the COPD mouse model (Supplementary Method 18, 19). b–d CS-treated MT i.p mice reveal alleviated airway inflammation as reflected by the b total cell counts, c neutrophil counts and d lymphocyte counts in the bronchoalveolar lavage fluid (BALF, Supplementary Method 22). e–h CS-treated MT i.p mice reveal overall reduced production of NF-κB-dependent inflammatory cytokines in the BALF (supplementary Method 22, 26): e C-X-C motif chemokine ligand 5 (CXCL5), f granulocyte-macrophage colony-stimulating factor (GM-CSF), g tumour necrosis factor-alpha (TNFα) and h interleukin 1β (IL-1β). i, j CS-treated MT i.p mice reveal reduced levels of j IL-12, but not i IFN-β, in the BALF, compared with CS-treated saline i.p mice. k, l CS-treated MT i.p mice reveal alleviated emphysema and airflow limitation in lung function tests (supplementary Method 21) as evaluated by k functional residual capacity/body weight (FRC/BW) and l forced expiratory volume at 100 ms/forced vital capacity (FEV100/FVC). m Representative images of hematoxylin-eosin (H&E)-stained lung slices display the decreased severity of airway inflammation in CS-treated MT i.p mice, compared with CS-treated saline i.p mice (scale bar: 100 μm, supplementary Method 23), as summarised in n histological score. o Representative immunofluorescence images reveal the decreased infiltration of NETs (co-stained with DNA, myeloperoxidase and histone H3) in lung slices of CS-treated MT i.p mice, compared with CS-treated saline i.p mice (scale bar: 100 μm, supplementary Method 24), as summarised in (p) normalised area of NETs