Objective: Interleukin 22 (IL-22) is produced mainly by T cells and recognized by mucosal receptors. IL-22 has been previously shown to increase hBD-2 and hBD-3 mRNA expression in primary and keratinocyte cell lines. Specifically, IL-22 receptors are elevated on keratinocytes following T cell-derived Interferon-γ (IFN-γ) stimulation. IL-22 signaling leads to STAT-3 activation and subsequent increases in hBD expression. In this study, we asked if human oral epithelial cells (HOECs) respond to IL-22 signaling by also upregulating hBD expression. We further examined the expression of hBD in-situ using confocal microscopy to localize hBD and IL-22 expression in both skin (psoriasis) and oral inflammatory diseases.

Methods: Both HOECs and an immortal oral keratinocyte cell line (TERT) were incubated with recombinant human IL-22 (rhIL-22) at various concentrations (0, 3, 10, 30, 100 ng/μl) for 18hr. Fusobacterium nucleatum was used as a positive control. Fold increases in mRNA expression of hBD-2 and hBD-3 in HOEC and TERT cells were quantified by real-time PCR (qPCR) analysis. Confocal microscopy was used to assess the localization of hBD-2 and hBD-3 in several oral and cutaneous skin diseases.

Results: rhIL-22 induced hBD-2 and hBD-3 expression in a dose dependant manner, with peak induction at 100ng/μL concentration. hBD-2 expression was 21 fold greater than control in HOECs, while hBD-3 expression was 18 fold greater than control in TERTs. Expression of hBD-3 appeared more localized to basal keratinocytes in both psoriatic and inflammatory oral dermatoses, while hBD-2 expression appeared more suprabasal.

Conclusion: rhIL-22 induces mRNA expression of HBD-2 and HBD-3 in HOECs, demonstrating the likely expression of IL-22R in resting oral keratinocytes. Primary HOECs express higher levels of hBD-2 mRNA compared to hBD-3 mRNA following IL-22 stimulation. In contrast, the immortalized TERT cell line exhibited higher levels of hBD-3 compared to hBD-2 following stimulation. Supported by NIH/NIDCR R01DE16334 and R01DE17334.

Back to the Microbiology / Immunology and Infection Control Program
Back to the IADR/AADR/CADR 85th General Session and Exhibition (March 21-24, 2007)

Top Level Search