Cigarette smoke-induced pulmonary inflammation is attenuated in CD69-deficient mice

Since microRNA (miR)-223-3p modulates inflammatory responses and COPD is associated with amplified pulmonary inflammation, we hypothesized that miR-223-3p plays a role in COPD pathogenesis. Expression of miR-223-3p was measured in lung tissue of 2 independent cohorts with COPD GOLD stage II-IV patients, never smokers and smokers without COPD. The functional role of miR-223-3p was studied in deficient mice and upon overexpression in airway epithelial cells from COPD and controls. We observed higher miR-223-3p levels in patients with COPD stage II-IV compared to (non)-smoking controls, and levels were associated with higher neutrophil numbers in bronchial biopsies of COPD patients. MiR-223-3p expression was also increased in lungs and bronchoalveolar lavage of cigarette smoke (CS)-exposed mice. CS-induced neutrophil and monocyte lung infiltration was stronger in miR-223 deficient mice upon acute (5 days) exposure, but attenuated upon sub-chronic (4 weeks) exposure. Additionally, miR-223 deficiency attenuated acute and sub-chronic CS-induced lung infiltration of dendritic cells and T lymphocytes. Finally, in vitro overexpression of miR-223-3p in non-COPD airway epithelial cells suppressed CXCL8 and GM-CSF secretion and gene expression of the pro-inflammatory transcription factor TRAF6. Importantly, this suppressive effect of miR-223-3p was compromised in COPD-derived cultures. In conclusion, we demonstrate that miR-223-3p is increased in lungs of COPD patients and CS-exposed mice, and is associated with neutrophilic inflammation. In vivo data indicate that miR-223 acts as negative regulator of acute CS-induced neutrophilic and monocytic inflammation. In vitro data suggests that miR-223-3p does so by suppressing pro-inflammatory airway epithelial responses, which is less effective in COPD epithelium.

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Cigarette smoke-induced pulmonary inflammation, but not airway remodelling, is attenuated in chemokine receptor 5-deficient mice

Clinical & Experimental Allergy ◽

10.1111/j.1365-2222.2007.02808.x ◽

2007 ◽

Vol 0 (0) ◽

pp. 070817170338002-??? ◽

Cited By ~ 6

Author(s):

K. R. Bracke ◽

A. I. D'hulst ◽

T. Maes ◽

I. K. Demedts ◽

K. B. Moerloose ◽

...

Keyword(s):

Cigarette Smoke ◽

Chemokine Receptor ◽

Pulmonary Inflammation ◽

Airway Remodelling ◽

Deficient Mice ◽

Chemokine Receptor 5

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Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice

Inflammation ◽

10.1007/s10753-016-0495-z ◽

2016 ◽

Vol 40 (2) ◽

pp. 497-510 ◽

Cited By ~ 17

Author(s):

Yunxiao Li ◽

Ganggang Yu ◽

Shaopeng Yuan ◽

Chunting Tan ◽

Puqiao Lian ◽

...

Keyword(s):

Cigarette Smoke ◽

Pulmonary Inflammation ◽

Deficient Mice

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Liquorice exaggerates protective action of Solanum xanthocarpum against cigarette smoke induced pulmonary inflammation

Planta Medica ◽

10.1055/s-0034-1382708 ◽

2014 ◽

Vol 80 (10) ◽

Author(s):

RA Manek ◽

NR Sheth ◽

JR Chavda ◽

JD Vaghasiya ◽

KP Modi ◽

...

Keyword(s):

Cigarette Smoke ◽

Protective Action ◽

Pulmonary Inflammation ◽

Solanum Xanthocarpum

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A 7-month inhalation toxicology study in C57BL/6 mice demonstrates reduced pulmonary inflammation and emphysematous changes following smoking cessation or switching to e-vapor products

Toxicology Research and Application ◽

10.1177/2397847321995875 ◽

2021 ◽

Vol 5 ◽

pp. 239784732199587

Author(s):

Ashutosh Kumar ◽

Ulrike Kogel ◽

Marja Talikka ◽

Celine Merg ◽

Emmanuel Guedj ◽

...

Keyword(s):

Smoking Cessation ◽

Cigarette Smoke ◽

Pulmonary Inflammation ◽

Clinical Signs ◽

Inhalation Study ◽

Toxicology Study ◽

Nasal Tissue ◽

Product Switching ◽

The Impact

Cigarette smoking causes serious diseases, including lung cancer, atherosclerotic coronary artery disease, peripheral vascular disease, chronic bronchitis, and emphysema. While cessation remains the most effective approach to minimize smoking-related disease, alternative non-combustible tobacco-derived nicotine-containing products may reduce disease risks among those unable or unwilling to quit. E-vapor aerosols typically contain significantly lower levels of smoke-related harmful and potentially harmful constituents; however, health risks of long-term inhalation exposures are unknown. We designed a 7-month inhalation study in C57BL/6 mice to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation (Cessation group) or switching to an e-vapor product (Switching group) after 3 months of exposure to 3R4F cigarette smoke (CS). There were no significant changes in in-life observations (body weights, clinical signs) in e-vapor groups compared to the Sham Control. The 3R4F CS group showed reduced respiratory function during exposure and had lower body weight and showed transient signs of distress post-exposure. Following 7 months of exposure, e-vapor aerosols resulted in no or minimal increase in pulmonary inflammation, while exposure to 3R4F CS led to impairment of lung function and caused marked lung inflammation and emphysematous changes. Biological changes observed in the Switching group were similar to the Cessation group. 3R4F CS exposure dysregulated the lung and nasal tissue transcriptome, while these molecular effects were substantially lower in the e-vapor group. Results from this study demonstrate that in comparison with 3R4F CS, e-vapor aerosols induce substantially lower biological responses including pulmonary inflammation and emphysematous changes, and that complete switching from CS to e-vapor products significantly reduces biological changes associated with CS in C57BL/6 mice.

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