Identifying the mechanisms underlying inflammation-induced lung maturation in the fetus
My research aims to identify the molecular pathways by which inflammation stimulates precocious surfactant production in the lungs of premature babies.
We want to understand the effect of inflammation on the cells of the developing alveoli in the fetal lung. By isolating lung cells from fetal mice, and growing them in tissue culture, we can treat the cells with factors that cause inflammation. Lipopolysaccharide (LPS) elicits an inflammatory reaction by activating the innate immune system. After treating the lung cells with LPS, we are able to assess the effect of the inflammation on the cells by measuring changes to the gene expression, particularly the surfactant proteins.
Our initial results suggest that inflammation directly on the distal lung epithelial cells does not alter surfactant protein gene expression, but is mediated by fetal lung fibroblast cells.
Why my research is important
More than 1 in 10 babies are born preterm worldwide, and the incidence is increasing. Respiratory disease resulting from lung immaturity is the major cause of morbidity and mortality of preterm babies because their lungs are structurally and biochemically immature. This commonly leads to respiratory distress syndrome (RDS) in preterm babies. The existing therapy to prevent preterm lung disease; antenatal corticosteroids administered to women in preterm labour, reduces the risk of RDS by only one third, and there are concerns about adverse life-long effects on health. Clearly a better therapy is needed to prevent preterm lung disease.
By unravelling the mechanisms by which inflammation alters fetal lung gene expression of surfactant proteins, we may find a target for future therapeutics to reduce the risk of RDS in babies born preterm.