Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response

Fatoumata B Sow; Jack M Gallup; David K Meyerholz; Mark R Ackermann

doi:10.1016/j.dci.2009.01.004

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Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response

Journal article

Peer reviewed

Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response

Fatoumata B Sow, Jack M Gallup, David K Meyerholz and Mark R Ackermann

Developmental and comparative immunology, Vol.33(6), pp.761-771

06/2009

DOI: 10.1016/j.dci.2009.01.004

PMCID: PMC2791060

PMID: 19189846

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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.

Humans

RNA, Messenger - analysis

Gene Expression Profiling

Respiratory Syncytial Virus Infections - immunology

Collectins - biosynthesis

Lung - virology

Polymerase Chain Reaction

Complement System Proteins - genetics

Collectins - metabolism

Cytokines - genetics

Vascular Endothelial Growth Factor A - pharmacology

Infant, Newborn

Respiratory Distress Syndrome, Newborn - immunology

Animals, Newborn

Chemokines - biosynthesis

Complement System Proteins - biosynthesis

Vascular Endothelial Growth Factor A - therapeutic use

Toll-Like Receptors - biosynthesis

Chemokines - genetics

Animals

Lung - drug effects

Toll-Like Receptors - genetics

Sheep

Cytokines - biosynthesis

Lung - immunology

Details

Title: Subtitle: Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response
Creators: Fatoumata B Sow - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. fsow@iastate.edu
Jack M Gallup
David K Meyerholz
Mark R Ackermann
Resource Type: Journal article
Publication Details: Developmental and comparative immunology, Vol.33(6), pp.761-771
DOI: 10.1016/j.dci.2009.01.004
PMID: 19189846
PMCID: PMC2791060
NLM abbreviation: Dev Comp Immunol
ISSN: 0145-305X
eISSN: 1879-0089
Publisher: Elsevier BV
Grant note: K08 AI055499 / NIAID NIH HHS R01 AI062787-05 / NIAID NIH HHS R01 AI062787 / NIAID NIH HHS
Language: English
Date published: 06/2009
Academic Unit: Pathology
Record Identifier: 9984083242902771

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