IL-6 Signaling in Gingival Epithelial Cells by Candida albicans Infection

Objectives: The presence of yeasts in periodontal pockets is well known, and Candida albicans is the most commonly isolated species from the oral cavity. The immune response and anticandidal activity of oral keratinocytes play a key role in host defense against C. albicans infection. It has been reported that C. albicans challenged IL-8 production in human gingival epithelial cells (HuGE), however, the molecular mechanism of C. albicans infection in periodontal diseases is unknown. To clarify the role of C. albicans in periodontitis, gene expression profiles in C. albicans-infected HuGE were monitored. Methods: Primary human gingival epithelial cells were cultured from healthy human gingival tissues, and stimulated with C. albicans ATCC90029 for 8 hrs. Total RNA was extracted and monitored mRNA levels using Affymetrix GeneChip (Human Genome U133 plus 2.0 array, ca. 47,000 genes). GeneChip data was analyzed by GeneSpring software and Ingenuity Pathway Analysis (IPA) system. Altered mRNA levels in GeneChip results were confirmed by RT-PCR and real-time PCR. Rat gingival tissues were challenged with C. albicans live cells, and gingival tissues were collected, and then immunohistochemical examination was carried out. Results: GeneChip results demonstrated that many gene expressions were altered by C. albicans, including up-regulated IL-6. IPA analysis reveals that IL-6 signal pathways is involved in activation of IL-8 production through NF-IL6. Strong immunoreactivity against IL-6 was observed in the rat gingival epithelium by C. albicans infection. Conclusion: C. albicans infection may contribute to the modulation of periodontitis through activation of the IL-6 signal pathway in gingival epithelium.