Human beta-defensin-2 in oral cancer with opportunistic Candida infection.
Candida albicans (CA) is a frequent opportunistic pathogen in cancer patients. Usually, human surfaces are protected, apart from physical barriers, by the production of human beta-defensins (hBD). hBD-2 shows a potent antimicrobial activity against CA. We therefore investigated whether CA induces hBD-2 expression in primary oral cells and if immunosuppressive betamethasone alters hBD-2 expression. Additionally, we studied, whether a lack of hBD-2 expression could explain opportunistic infection of tonsillar cancer. Primary oral epithelial cells and fibroblasts were stimulated with Candida albicans in a time- and dose-dependent manner with or without betamethasone preincubation. Total RNA from oral cells and specimens was isolated and hBD-2 expression was analyzed by semiquantitative RT-PCR. Our data demonstrate that opportunistic CA induced hBD-2 expression in a time- and dose-dependent manner, suggesting hBD-2 to be a fast antifungal, epithelia-derived immune response. Treatment with glucocorticoid could lead to diminished innate immunity based on suppression of inducible AP. Malignant transformation induces alteration of hBD-2 expression and leads to a reduced hBD-2 expression and subsequentially to Candida colonization on oral SCCs.
Meyer
Jens Eduard
JE
Department of Otorhinolaryngology, Head and Neck Surgery, University of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. jmeyer@hno.uni-kiel.de
Harder
Jürgen
J
Görögh
Tibor
T
Weise
Jan Bernd
JB
Schubert
Sabine
S
Janssen
Dirk
D
Maune
Steffen
S
D001483:Base Sequence; D001623:Betamethasone / Q000494:pharmacology; D002177:Candidiasis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D008969:Molecular Sequence Data; D009894:Opportunistic Infections / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D014066:Palatine Tonsil / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014067:Tonsillar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D014407:Tumor Cells, Cultured; D023083:beta-Defensins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
C106641:DEFB4A protein, human; D012333:RNA, Messenger; D023083:beta-Defensins; D001623:Betamethasone