title: 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.
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 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.
  
  
  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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. nadine@steubesand.org
authors.forename: Nadine
authors.initials: N
authors.lastname: Steubesand
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Kiehne
authors.forename: Gabriele
authors.initials: G
authors.lastname: Brunke
authors.forename: Rene
authors.initials: R
authors.lastname: Pahl
authors.forename: Karina
authors.initials: K
authors.lastname: Reiss
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
authors.forename: Sabine
authors.initials: S
authors.lastname: Schubert
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Fölsch
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Alexander
authors.initials: A
authors.lastname: Arlt
mesh_terms: D002176:Candida albicans / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D018920:Coculture Techniques; D024202:Electrophoretic Mobility Shift Assay; D066246:ErbB Receptors / Q000378:metabolism; D004941:Esophagitis; D004947:Esophagus / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019899:Paracrine Communication; D015398:Signal Transduction / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014774:Virulence; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D023083:beta-Defensins; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases