Journal article
Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus
American journal of respiratory and critical care medicine, Vol.194(7), pp.845-854
10/01/2016
DOI: 10.1164/rccm.201510-2112OC
PMCID: PMC5074652
PMID: 27027566
Abstract
Rationale:
Studies suggest that inappropriate responses to proinflammatory stimuli might contribute to inflammation in cystic fibrosis (CF) lungs. However, technical challenges have made it difficult to distinguish whether altered responses in CF airways are an intrinsic defect or a secondary effect of chronic disease in their tissue of origin. The CF pig model provides an opportunity to study the inflammatory responses of CF airways at birth, before the onset of infection and inflammation.
Objectives:
To test the hypothesis that acute inflammatory responses are perturbed in porcine CF airways.
Methods:
We investigated the inflammatory responses of newborn CF and non-CF pig airways following a 4-hour exposure to heat-killed
Staphylococcus aureus, in vivo
and
in vitro
.
Measurements and Main Results:
Following an
in vivo S. aureus
challenge, markers of inflammation were similar between CF and littermate control animals through evaluation of bronchoalveolar lavage and tissues. However, transcriptome analysis revealed genotype-dependent differences as CF pigs showed a diminished host defense response compared with their non-CF counterparts. Furthermore, CF pig airways exhibited an increase in apoptotic pathways and a suppression of ciliary and flagellar biosynthetic pathways. Similar differences were observed in cultured airway epithelia from CF and non-CF pigs exposed to the stimulus.
Conclusions:
Transcriptome profiling suggests that acute inflammatory responses are dysregulated in the airways of newborn CF pigs.
Details
- Title: Subtitle
- Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus
- Creators
- Jennifer A Bartlett - Department of PediatricsShyam Ramachandran - Department of PediatricsChristine L Wohlford-Lenane - Department of PediatricsCarrie K Barker - Department of PediatricsAlejandro A Pezzulo - Department of Internal MedicineJoseph Zabner - Department of Internal MedicineMichael J Welsh - Department of Internal MedicineDavid K Meyerholz - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IowaDavid A Stoltz - Department of Internal MedicinePaul B McCray - Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.194(7), pp.845-854
- DOI
- 10.1164/rccm.201510-2112OC
- PMID
- 27027566
- PMCID
- PMC5074652
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 10/01/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020786202771
Metrics
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