Effect of rhCC10 on the Pro/Anti-Inflammatory Profile of the Immature Lung

Abstract

There is a gap in the treatment of preterm infants with respiratory distress syndrome. Despite addressing surfactant insufficiency and mechanical instability, currently available exogenous surfactant does not reduce the inflammation that results from aggressive ventilation and hyperoxia. Preterm infants are also deficient in anti-oxidant and anti-inflammatory defenses. All of these factors predispose the infant to bronchopulmonary dysplasia. Recombinant human Club Cell Secretory Protein 10 (rhCC10), known to inhibit sPLA2, has been used to reduce ventilator induced lung inflammation. The long-term goal of this study is to understand the impact of rhCC10 on the pro/anti-inflammatory balance during early development. We will interrogate the link between Toll-Like Receptors (TLR 4) and rhCC10 because TLRs are integral to lung inflammation. By measuring the mRNA expression, protein, and downstream signaling activity in rhCC10 treated preterm lamb lung and then in A549 cells, an alveolar epithelial cell-like system, the anti-inflammatory effect of rhCC10 will be differentiated. This research is significant because it will improve understanding of the effect of rhCC10 on pro/anti-inflammatory regulation and provide insight regarding potential co-therapies when treating with rhCC10.