IL-6 Signaling in Candida albicans-infected Human Gingival Epithelial Cells

The presence of yeasts in periodontal pockets is well known and Candida albicans is the species most commonly isolated from the oral cavity. The immune response and anticandidal activity of oral epithelium cells play a key role in the host defense against C. albicans infection. An increased induction of IL-8 in human gingival epithelial cells (HGE) by C. albicans infection has been investigated. In the present study, to clarify the role of C. albicans in periodontitis, gene expression profiles in C. albicans-infected HGE were monitored using DNA microarray and the IL-6 signal pathway was further analyzed using the Ingenuity Pathway Analysis system. Human gingival epithelial cells were primarily cultured from healthy human gingival tissues and challenged with C. albicans ATCC90029. After 8 hours, total RNA was extracted and mRNA levels were monitored using Affymetrix GeneChip (Human Genome U133 plus 2.0 Array, ca. 47,000 genes). GeneChip data were analyzed by GeneSpring software and the IPA system. IL-6, IL-6R, IL-6ST, NF-IL6, and IL-8 genes were up-regulated to over twice the level in HGE by C. albicans infection. Altered mRNA levels in GeneChip results were confirmed by reverse transcription polymerase chain reaction (RT-PCR) and real-time RT-PCR. Rat gingiva was infected with C. albicans cells and immunohistochemical examination for IL-6 production was carried out. Stronger immunoreactivity against IL-6 was observed in the rat gingival epithelium infected with C. albicans. These findings suggest that IL-6 signal pathways are involved in the activation of IL-8 production.