Mechanism of autophagy in a newborn responsible for deleterious effect of air pollutants

Both exposure to nitrogen dioxide (NO₂) and particulate matter smaller than 10 microns in diameter (PM₁₀) during pregnancy initiate processes of autophagy and senescence in a newborn. A study showed that exposure to NO₂ was associated with an increase in the protein Beclin-1, a key stimulator of autophagy.
Earlier work by Dr Olga Gorlanova (University of Basel, Switzerland) has shown that exposure to air pollution during pregnancy could affect lung function and the immune system in newborns [1]. However, the cellular mechanisms of the deleterious effect of air pollutants on the respiratory health of infants are largely unknown. “Autophagy is a physiological process that helps cells to fight oxidative stress damage,” Dr Gorlanova explained [2]. Air pollution exposure leads to an oxidative stress response in the foetus that may initiate autophagy. Degradation of damaged cell components can then lead to senescent cells that produce different senescence-associated secretory phenotypes (so-called SASP), consisting of cytokines, chemokines, metalloproteinases, and growth factors. SASP can promote remodelling, inflammation, infectious susceptibility, angiogenesis, and proliferation while hindering tissue repair and regeneration.
With her study, Dr Gorlanova wanted to shed light on the association between NO₂ and PM₁₀ exposure during pregnancy and a predefined set of autophagy-related biomarkers obtained from the cord blood of healthy-term newborns. Based on the autophagy/SASP biomarker profile, the researchers tried to find out whether all infants respond to air pollution in the same way.
The study population consisted of healthy-term newborns (n=449) from the Basel-Bern Infant Lung Development (BILD) cohort. The BILD study started in 1999 in Bern and aims to recruit 1,000 babies by 2025. The aim of the study is to investigate the effects of genetics and the environment (particularly air pollution) on lung development in babies and children.
Analysis of 11 proteins in the cord blood, including Beclin-1, SIRT1, different cytokines, and metalloproteinases was performed and related to the air pollutant exposure.
Exposure to NO₂ was associated with an increase in the protein Beclin-1 and a decrease in SIRT1 and IL-8. Beclin-1 is a protein that is central to initiating autophagy whereas SIRT1 play a protective role in stress resistance, inflammation, and ageing. Another important study result was that newborns from the cluster with low air pollution exposure had low levels of autophagy, senescence, inflammatory cytokines, and remodelling SASP proteins.
“Autophagy may play a role in the defence against oxidative stress damage related to pre-natal air pollution exposure in newborns. In addition, there is a dose-dependent relationship between pre-natal air pollution and autophagy-related biomarkers,” Dr Gorlanova concluded.

1. Gorlanova O, et al. Pediatr Allergy Immunol 2023;34:e13902.
2. Gorlanova O. Profiles of pregnancy and early-life urban and lifestyle exposures and respiratory health in children. Abstract 4941, ERS International Congress 2023, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023