Cigarette smoke alters inflammatory genes and the extracellular matrix — investigations on viable sections of peripheral human lungs

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex chronic respiratory disorder often caused by cigarette smoke. Cigarette smoke contains hundreds of toxic substances. In our study, we wanted to identify initial mechanisms of cigarette smoke induced changes in the distal lung. Viable slices of human lungs were exposed 24 h to cigarette smoke condensate, and the dose–response profile was analyzed. Non-toxic condensate concentrations and lipopolysaccharide were used for further experiments. COPD-related protein and gene expression was measured. Cigarette smoke condensate did not induce pro-inflammatory cytokines and most inflammation-associated genes. In contrast, lipopolysaccharide significantly induced IL-1α, IL-1β, TNF-α and IL-8 (proteins) and IL1B, IL6, and TNF (genes). Interestingly, cigarette smoke condensate induced metabolism- and extracellular matrix–associated proteins and genes, which were not influenced by lipopolysaccharide. Also, a significant regulation of CYP1A1 and CYP1B1, as well as MMP9 and MMP9/TIMP1 ratio, was observed which resembles typical findings in COPD. In conclusion, our data show that cigarette smoke and lipopolysaccharide induce significant responses in human lung tissue ex vivo, giving first hints that COPD starts early in smoking history.

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients

“…Smoking harms the lungs by inciting chronic inflammation and oxidative stress, thus worsening the progression of IPF [32][33][34][35]. It leads to persistent inflammation, disrupts the balance of oxidation, contributes to the buildup of extracellular matrix in the lungs, impairs lung function, hampers gas exchange, and accelerates the deterioration of IPF [32,36]. Exposure to CS or its extract (CSE) results in the senescence of alveolar epithelial type 2 (AT2) cells, a pivotal process in the progression of lung fibrosis [37].…”

The COPD GWAS gene ADGRG6 instructs function and injury response in human iPSC-derived type II alveolar epithelial cells

“…In future work, it will be interesting to determine whether GPR126 coordinates epithelial responses to other proinflammatory insults, such as lung infections. Cigarette smoke alters the composition of the ECM, 51 raising the possibility that GPR126 activation may be modulated by the effects of smoke inhalation on activating ligands. Finally, our findings demonstrate that ADGRG6 -kd iAT2s are more proliferative and better able to form colonies following cigarette smoke injury.…”

Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery

“…In addition to noxious gases, exposure to environmental cigarette smoke (CS), has been studied in PCLS. CS or CSE (cigarette smoke extract) elicited inflammatory mediator release, induced histologic inflammatory changes and extracellular matrix gene expression, decreased cell viability, increased markers of the unfolded protein response, and increased airway constriction to serotonin but not methacholine [246][247][248][249]. Interestingly, menthol-containing e-cigarette condensate decreased airway contraction in PCLS but increased oxidative stress markers [250].…”