Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response
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Published on: October 25, 2015
Fatoumata B Sow1, Jack M Gallup, David K Meyerholz
1Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. fsow@iastate.edu
Insights
Vascular Endothelial Growth Factor (VEGF) enhances neonatal lung immune responses by upregulating key immune genes. This suggests VEGF could be a potential therapy for respiratory distress syndrome (RDS) in preterm infants.
Area of Science:
- Neonatal immunology
- Pulmonary medicine
- Molecular biology
Background:
- Preterm neonates are susceptible to respiratory distress syndrome (RDS) due to immature lung surfactant.
- Glucocorticoids (GCs) improve lung development but have uncertain safety and unclear mechanisms.
- Vascular Endothelial Growth Factor (VEGF) previously showed potential in enhancing innate immunity and reducing respiratory syncytial virus (RSV) severity.
Purpose of the Study:
- To investigate the effects of VEGF administration on local immune responses in neonatal lambs.
- To test the hypothesis that VEGF induces genes crucial for host immune responses in the lung.
Main Methods:
- Utilized neonatal lambs, whose lungs resemble human lungs in development and immune response.
- Analyzed global gene expression profiles in lamb lungs post-VEGF treatment using real-time quantitative PCR (qPCR).
Main Results:
- VEGF administration significantly induced the expression of various immune-related genes.
- Upregulated genes included chemokines (IL-8, RANTES, MCP-1), cytokines (IFN-gamma, IL-6, TNF-alpha, GMCSF), Toll-like receptor (TLR)-4, complement factors (C3, CFB, CFH), and collectins (SP-A, SP-D).
Conclusions:
- VEGF effectively regulates local immune gene expression in vivo.
- VEGF warrants further exploration as a potential exogenous therapy for neonatal lung diseases, including RDS.
Abstract:
Preterm and young neonates have an increased predisposition to respiratory distress syndrome (RDS) associated with an immature development of lung surfactant. Glucocorticoids (GCs) are the major immunomodulatory agents used to increase lung development and reduce the mortality and morbidity of preterm infants with RDS. However, their safety remains uncertain, and the precise mechanisms by which they improve lung function are unclear. In previous studies, we found that vascular endothelial growth factor (VEGF) enhances the innate immune response by respiratory epithelial cells, causes a monocytic infiltration into the lung, and reduces the severity of infection by respiratory syncytial virus (RSV), a respiratory pathogen known to affect preterm infants at a high prevalence. The purpose of this study is to measure the effects of VEGF administration on local immune responses in neonatal lambs, as the ovine lung is well suited for comparison to the human lung, due to similarities in alveolar development, immune responses, and RSV susceptibility. We hypothesized that VEGF induces the expression of genes necessary for host immune responses. We analyzed global gene expression profiles in the lungs of neonate lambs treated with VEGF by real-time qPCR. We report that VEGF induced the expression of chemokines (IL-8, RANTES, MCP-1), cytokines (IFN-gamma, IL-6, TNF-alpha, GMCSF), Toll-like receptor (TLR)-4, complement family members (C3, CFB, CFH) and collectins (SP-A, SP-D). These results suggest that VEGF can regulate local immune gene expression in vivo and should be further explored as a potential exogenous therapy for various lung diseases.
