Abstract
Background:
Defensins are antimicrobial peptides expressed on mucosal surfaces that contribute to maintaining intestinal homeostasis by providing innate defense mechanisms for the epithelia. Defensin expression is altered in a number of diseases that affect mucosal surfaces, such as atopic dermatitis, allergic rhinitis, and inflammatory bowel disease. Similar to atopic dermatitis, eosinophilic esophagitis (EoE) is a chronic disease in which the squamous epithelial surface is affected by a similar TH2 microenvironment and eosinophil-predominant inflammation. Therefore, we hypothesized that defensin expression would be decreased in EoE.
Methods:
To address this, we measured defensin expression in vitro in cell lines derived from patients with EoE (EoE1-T) or gastroesophageal reflux disease (GERD) (NES-G4T cells) and ex vivo in esophageal mucosal biopsy samples from children with EoE or GERD and control children without esophageal disease.
Results:
Interleukin-5 induced a decrease in human β-defensin (hBD) -1 and hBD3 expression in EoE1-T but not in NES-G4T cells. Compared with esophageal biopsy specimens from GERD and control children, specimens from EoE pediatric patients revealed a significant decrease in mRNA and protein expression for hBD1 and hBD3.
Conclusion:
Diminished expression of hBD1 and hBD3 may make the esophageal epithelium more susceptible to the development and/or perpetuation of EoE.
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Acknowledgements
We thank Caleb Kelly for his technical support with in vitro experiments. We thank the physicians (Robert Kramer, Edward Hoffenberg, Edwin Liu, Edwin de Zoeten, Shikha Sundaram, Cara Mack, Michael Narkewicz, Ronald Sokol, Jason Soden, Deborah Neigut, David Brumbaugh, and Christine Waasdorp Hurtado), nurses (Tamela Armstrong and Jo Anne Newton), and technical staff (Bill Marcovich) who contributed to this work by helping to collect samples and enrolling subjects. We are grateful to our patients and families who consented to be a part of this study.
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Schroeder, S., Robinson, Z., Masterson, J. et al. Esophageal human β-defensin expression in eosinophilic esophagitis. Pediatr Res 73, 647–654 (2013). https://doi.org/10.1038/pr.2013.23
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DOI: https://doi.org/10.1038/pr.2013.23
