Asthma susceptibility in prenatal nicotine-exposed mice attributed to ß-catenin increase during CD4+ T cell development.
Ecotoxicol Environ Saf
; 238: 113572, 2022 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-35533447
ABSTRACT
Cigarette smoke is a common global environmental pollutant. Asthma, the most frequent allergic airway disease, is related to maternal exposure to cigarette smoke. Our previous studies demonstrated that prenatal exposure to nicotine (PNE), the major active product of smoking, impairs fetal thymopoiesis and CD4+ T cell development after birth. This study aimed to investigate whether PNE contributes to asthma susceptibility through CD4+ T cell development alterations. First, A PNE model was established by administering 3 mg/kg/day nicotine to maternal mice, and then an ovalbumin-induced asthma model was established in the offspring. Further, ß-catenin and downstream pathways were inhibited in vitro to confirm the molecular mechanisms underlying the phenotype observed during the in vivo phase. The results showed that PNE induced Th2 and Th17 biases at developmental checkpoints and aggravated asthma symptoms in the offspring. In fetuses, PNE up-regulated α7 nAChR, activated PI3K-AKT, promoted ß-catenin level increase, and established potential Th2- and Th17-biased gene expression patterns during thymopoiesis, which persisted after birth. Similar results were also observed in 1 µM nicotine-treated thymocytes in vitro. Moreover, inhibiting PI3K-AKT by LY294002 abrogated nicotine-mediated ß-catenin level increase and thymopoiesis abnormalities, and an α7 nAChR antagonist (α-btx) also reversed nicotine-induced PI3K-AKT activation. Our findings provide strong evidence that PNE is a risk factor for T cell deviation and postnatal asthma, and revealed that nicotine-induced ß-catenin level increase induces thymopoiesis abnormalities.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Efectos Tardíos de la Exposición Prenatal
/
Asma
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
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Humans
/
Pregnancy
Idioma:
En
Revista:
Ecotoxicol Environ Saf
Año:
2022
Tipo del documento:
Article
País de afiliación:
China