Research article

The expression of the β-defensins hBD-2 and hBD-3 is differentially regulated by NF-κB and MAPK/AP-1 pathways in an in vitro model of Candida esophagitis

Nadine Steubesand¹ , Karlheinz Kiehne¹ , Gabriele Brunke¹ , Rene Pahl¹ , Karina Reiss³ , Karl-Heinz Herzig⁴ , Sabine Schubert⁵ , Stefan Schreiber^1,2 , Ulrich R Fölsch¹ , Philip Rosenstiel² and Alexander Arlt¹

¹  Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

²  Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

³  Department of Department of Dermatology and Allergology; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

⁴  Institute of Biomedicine, Div of Physiology, and Biocenter of Oulu, University of Oulu, and Department of Internal Medicine, University of Kuopio, Finland

⁵  Institute for Infection Medicine; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

author email corresponding author email

BMC Immunology 2009, 10:36doi:10.1186/1471-2172-10-36

Published:	12 June 2009

Abstract

Background

Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions it may cause life-threatening infections like Candida sepsis. Human β-defensins (hBDs) are critical components of host defense at mucosal surfaces and we have recently shown that hBD-2 and hBD-3 are upregulated in Candida esophagitis. We therefore studied the role of Candidate signalling pathways in order to understand the mechanisms involved in regulation of hBD-expression by C. albicans. We used the esophageal cell line OE21 and analysed the role of paracrine signals from polymorphonuclear leukocytes (PMN) in an in vitro model of esophageal candidiasis.

Results

Supernatants of C. albicans or indirect coculture with C. albicans induces upregulation of hBD-2 and hBD-3 expression. PMNs strongly amplifies C. albicans-mediated induction of hBDs. By EMSA we demonstrate that C. albicans activates NF-κB and AP-1 in OE21 cells. Inhibition of these pathways revealed that hBD-2 expression is synergistically regulated by both NF-κB and AP-1. In contrast hBD-3 expression is independent of NF-κB and relies solely on an EGFR/MAPK/AP-1-dependent pathway.

Conclusion

Our analysis of signal transduction events demonstrate a functional interaction of epithelial cells with PMNs in response to Candida infection involving divergent signalling events that differentially govern hBD-2 and hBD-3 expression.