ADAM33 is involved in post-natal airway hyperresponsiveness caused by maternal allergic airway inflammation

Wandel, Marieke, Davies, Elizabeth R, Kelly, Joanne, Freda Carmichael, Holgate, Stephen T, Whitsett, Jeffrey A., Davies, Donna E and Haitchi, Hans Michael (2018) ADAM33 is involved in post-natal airway hyperresponsiveness caused by maternal allergic airway inflammation. European Respiratory Society (ERS) International Congress 2018, , Paris, France. 15 - 19 Sep 2018. 132 PA1307 .

Abstract

Maternal allergy is a strong risk factor for developing asthma and airway hyperresponsiveness (AHR). The asthma susceptibility gene ADAM33 is associated with AHR and impaired lung function in early life. Our aim was to investigate gene-environment interactions involving Adam33 by determining the effects of maternal murine allergic airway inflammation on the lungs of offspring. We hypothesised that this will be modified in Adam33 knock out (KO) compared to wild-type (WT) offspring.

Allergic airway inflammation was induced by exposure to house dust mite (HDM) allergen in pregnant heterozygous Adam33 mice. WT and KO offspring from the same litters were studied on embryonic day (ED)17.5 and 2 and 4 weeks post partum. Lung function was performed in response to methacholine, bronchoalveolar lavage fluid (BALF) collected for differential cell counts and lung tissue for RTqPCR.

Compared with saline challenged mothers, 4-week-old WT offspring of HDM challenged mothers showed significantly enhanced AHR; KO offspring of HDM challenged mothers were protected against development of AHR. No inflammatory genes were up-regulated in the lungs and no inflammatory cells were present in the BALF at 2 or 4 weeks. While typical remodelling genes were not up-regulated at the time points studied, Adam33 mRNA expression was significantly increased in WT lungs at ED17.5 and Cholinergic Receptor Muscarinic 1 (Chrm1) mRNA at 4 weeks in offspring of HDM challenged mothers.

This study identifies an in utero gene-environment interaction involving ADAM33 that has implications for the development of AHR in early life. Further studies are needed to elucidate the mechanisms whereby ADAM33 mediates this.

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Contributors

Author: Elizabeth R Davies

Author: Donna E Davies

Author: Hans Michael Haitchi

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