Induction model (in vitro) | Induction model (in vivo) | Significant findings | Ref. |
CSE treatment: A549 cells CSE treatment: BEAS-2B cells | TRP ion channels, TRPA1 and TRPV1, mediate CSE-induced damage of bronchial and alveolar epithelial cells via modulation of oxidative stress, inflammation and mitochondrial damage. | [59] | |
CSE/LPS treatment: MDM cells CSE/LPS treatment: THP-1 cells | Increased caspase-1 activity via an NLRP3-independent and TLR4–TRIF–caspase-8-dependent pathway. | [60] | |
CSE treatment: 16HBE cells | CS exposure: male C57BL/6J mice, 30 days, with twice LPS (30 μg per 6 μL) intratracheal instillation | CSE-induced inflammation and contributed to pyroptosis through the ROS–NLRP3–caspase-1 pathway in 16HBE cells. | [52] |
CSE treatment: NCI-H292, 16HBE, NHBE cells CSE treatment: THP-1 cells, MDM cells | CSE- and eHSP70-induced ATP secretion and differential activation of NLRP3 inflammasome. | [61] | |
CSE treatment: THP-1 cells, MDM cells | CS exposure: male C57BL/6 mice, 6 months exposure | CSE decreased NLRP3 protein abundance via increased ubiquitin-mediated proteasomal processing. The release of IL-1β and IL-18 was also decreased with CSE. Provides mechanistic insights on immunosuppression in smokers. | [62] |
CSE treatment: THP-1 cells | CS exposure: C57BL/6 mice, 5 weeks exposure | CS repressed central components of the innate immune response to inhaled asbestos. | [63] |
CSE treatment: THP-1 cells | MyD88 inhibition markedly attenuated the expression of NLRP3 markers (NLRP3, caspase-1, IL-1β and IL-18), IL-6, SOCS3 and NF-κB. | [64] | |
CSE/LPS treatment: A549 cells | NLRP3 inflammasome is upregulated in COPD exacerbation and novel biomarkers for COPD exacerbation. | [65] | |
CS exposure: male C57BL/6 mice (wild type, ASC−/–, NALP3−/–, IPAF−/–, IL-1β−/–, IL-1α−/–, IL-18−/–, IL-18R–/–, caspase-1/11–/– and caspase-11–/–), 3 days LPS (1 mg·mL–1) aerosol for 30 min | A key role for the P2X7–NALP3–ASC–caspase-1/11–IL-1β–IL-18 axis in CS-induced airway inflammation. | [9] | |
Fresh-frozen lung tissues from COPD patients and healthy CS exposure: NLRX1−/– mutant mice and wild-type mice, exposure 3 months | CS-dependent NLRX1 inhibition facilitates MAVS/RHL activation and subsequent inflammation, remodelling, protease, cell death, and inflammasome responses. | [66] | |
CS exposure: female BALB/c mice, exposure 6 weeks plus gestation and lactation periods | Maternal CSE had adverse impacts on the male offspring's lungs, which were partially alleviated by maternal L-carnitine supplementation. Females were less affected by the adverse effects of maternal CSE. | [67] | |
CSE treatment: RAW264.7 cells | CS exposure: male C57BL/6J mice, exposure 15 weeks | TREM-1 promoted the lung injury and inflammation in COPD mouse through activation of NLRP3 inflammasome-mediated pyroptosis. A novel mechanism of TREM-1 in COPD development. | [68] |
CSE treatment: RAW 264.7 cells LPS treatment: RAW 264.7 cells DEP treatment: RAW 264.7 cells | PPE (15 μg per 50 μL) intratracheal instillation: C57BL/6 female mice | The NLRP3 inflammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model. NAC inhibits this activation. | [69] |
UFP treatment: COPD and non-COPD PBMCs UFP treatment: smoker and non-smoker PBMCs | Combustion-generated UFPs induced the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects. | [70] | |
CS exposure: SD rats for 2 months with twice LPS (200 μg per 100 μL) intratracheal instillation | SIRT1 attenuated apoptosis and ER stress in the lung tissues. A positive correlation was identified between SIRT1 and oxygen regulated protein 150. | [71] |
16HBE: human airway epithelial cell; A549: alveolar epithelial cell; ASC: apoptosis-associated speck-like protein containing a caspase recruitment domain; BEAS-2B: human bronchial epithelial cell; CSE: cigarette smoke extract; DEP: diesel exhaust particle; ER: endoplasmic reticulum; eHSP70: extracellular heat shock protein 70kDa; IL: interleukin; IPAF: interleukin converting enzyme protease activating factor; LPS: lipopolysaccharide; MAVS: mitochondrial antiviral signalling protein; MDM: human monocyte-derived macrophage; NAC: N-acetylcysteine (an ROS scavenger); NALP3: NACHT, LRR and PYD domains-containing protein 3; NCI-H292: human lung mucoepidermoid carcinoma cell; NF-κB: nuclear factor-κB; NHBE: normal human bronchial epithelial cell; NLRP3: nucleotide-binding oligomerisation domain-like receptor family, pyrin domain containing protein-3; NLRX1: nucleotide-binding oligomerisation domain, leucine rich repeat containing X1; PBMC: human peripheral blood mononuclear cell; PPE: porcine pancreatic elastase; RAW 264.7: mouse macrophage; RHL: RIG-I-like helicase; ROS: reactive oxygen species; SD: Sprague Dawley; SIRT1: sirtuin 1; SOCS3: suppressor of cytokine signalling 3; THP-1: monocytic leukaemic cell line; TLR: Toll-like receptor; TREM-1: triggering receptor expressed on myeloid cells 1; TRIF: TIR-domain-containing adaptor-inducing interferon-β; TRP: transient receptor potential protein; TRPA1: transient receptor potential cation channel, subfamily A, member 1; TRPV1: transient receptor potential cation channel subfamily V member 1; UFP: ultrafine particulate.