Early life exposure to nicotine modifies lung gene response after elastase-induced emphysema.

Blaskovic, Sanja; Donati, Yves; Ruchonnet-Metrailler, Isabelle; Avila, Yannick; Schittny, Dominik; Schlepütz, Christian Matthias; Schittny, Johannes; Barazzone-Argiroffo, Constance (2022). Early life exposure to nicotine modifies lung gene response after elastase-induced emphysema. Respiratory research, 23(1), p. 44. BioMed Central 10.1186/s12931-022-01956-4

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BACKGROUND

Chronic obstructive pulmonary disease (COPD) is among the top 5 causes of mortality in the world and can develop as a consequence of genetic and/or environmental factors. Current efforts are focused on identifying early life insults and how these contribute to COPD development. In line with this, our study focuses on the influence of early life nicotine exposure and its potential impact on (a) lung pulmonary functions, and (b) elastase-induced emphysema in adulthood.

METHODS

To address this hypothesis, we developed a model of 2 hits, delivered at different time points: mouse pups were first exposed to nicotine/placebo in utero and during lactation, and then subsequently received elastase/placebo at the age of 11 weeks. The effect of nicotine pretreatment and elastase instillation was assessed by (a) measurement of pulmonary function at post-elastase day (ped) 21, and (b) transcriptomic profiling at ped3 and 21, and complementary protein determination. Statistical significance was determined by 3- and 2-way ANOVA for pulmonary functions, and RNAseq results were analyzed using the R project.

RESULTS

We did not observe any impact of nicotine pre- and early post-natal exposure compared to control samples on lung pulmonary functions in adulthood, as measured by FLEXIVENT technology. After elastase instillation, substantial lung damage was detected by x-ray tomography and was accompanied by loss in body weight at ped3 as well as an increase in cell numbers, inflammatory markers in BAL and lung volume at ped21. Lung functions showed a decrease in elastance and an increase in deep inflation volume and pressure volume (pv) loop area in animals with emphysema at ped21. Nicotine had no effect on elastance and deep inflation volume, but did affect the pv loop area in animals with emphysema at ped21. Extensive transcriptomic changes were induced by elastase at ped3 both in the nicotine-pretreated and the control samples, with several pathways common to both groups, such as for cell cycle, DNA adhesion and DNA damage. Nicotine pretreatment affected the number of lymphocytes present in BAL after elastase instillation and some of the complement pathway related proteins, arguing for a slight modification of the immune response, as well as changes related to general body metabolism. The majority of elastase-induced transcriptomic changes detected at ped3 had disappeared at ped21. In addition, transcriptomic profiling singled out a common gene pool that was independently activated by nicotine and elastase.

CONCLUSIONS

Our study reports a broad spectrum of transient transcriptomic changes in mouse emphysema and identifies nicotine as influencing the emphysema-associated immune system response.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Blaskovic, Sanja; Schittny, Dominik Christian and Schittny, Johannes

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1465-9921

Publisher:

BioMed Central

Language:

English

Submitter:

Pubmed Import

Date Deposited:

07 Mar 2022 09:26

Last Modified:

20 Mar 2022 01:57

Publisher DOI:

10.1186/s12931-022-01956-4

PubMed ID:

35241086

Uncontrolled Keywords:

Emphysema Lung development Nicotine

BORIS DOI:

10.48350/166597

URI:

https://boris.unibe.ch/id/eprint/166597

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