In vitro mechanisms of interleukin-8-mediated responses of human gingival epithelial cells to Candida albicans infection.

Oral epithelial cells significantly influence host inflammatory responses against Candida albicans in oropharyngeal candidiasis. We sought to elucidate the pattern of interleukin-8 (IL-8) expression by oral epithelial cells, which may function as an early innate immune system mediator during C. albicans infection. Primary human gingival epithelial cells (HGECs) were co-cultured with either viable or heat-killed C. albicans or fungal-derived substances, such as fungal secretion, fungal extracted proteins, and alpha-mannan. In vitro cell injury due to viable C. albicans was detectable by an adenosine triphosphate-based assay after 12h of infection. Prior to the detection of cell injury, HGECs clearly increased production of interleukin-1 alpha (IL-1alpha) and IL-8 in response to C. albicans infection, as determined by enzyme-linked immunosorbent assay and real-time reverse transcription PCR. High concentrations of a suspension of heat-killed yeast and all fungal-derived substances examined also stimulated IL-8 production by HGECs. Incubation with neutralizing anti-IL-1alpha or anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies (mAb) significantly inhibited C. albicans-induced IL-8 production. Use of mAbs against both IL-1alpha and ICAM-1 produced a more significant combined inhibitory effect on the IL-8 production than either mAb alone. These findings indicate that HGECs synthesize increased levels of IL-1alpha and IL-8 in response to viable C. albicans before cell injury is manifested. Fungal cell-wall components, alpha-mannan, and fungal protein extracts are all sufficient to increase IL-8 production. The molecular mechanisms governing the IL-8 response of HGECs to C. albicans infection likely involve multiple converging signal transduction pathways, including those mediated by IL-1alpha and ICAM-1 activation.