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

Authors:
Nadine Steubesand, Karlheinz Kiehne, Gabriele Brunke, Rene Pahl, Karina Reiss, Karl-Heinz Herzig, Sabine Schubert, Stefan Schreiber, Ulrich R Fölsch, Philip Rosenstiel, Alexander Arlt
Year of publication:
2009
Volume:
10
Issue:
-
Issn:
1471-2172
Journal title abbreviated:
BMC IMMUNOL
Journal title long:
BMC immunology
Impact factor:
2.485
Abstract:
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 beta-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.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-kappaB and AP-1 in OE21 cells. Inhibition of these pathways revealed that hBD-2 expression is synergistically regulated by both NF-kappaB and AP-1. In contrast hBD-3 expression is independent of NF-kappaB and relies solely on an EGFR/MAPK/AP-1-dependent pathway.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.