Effects of tacrolimus on an organotypic raft-culture model mimicking oral mucosa

Background. Tacrolimus ointment has shown efficacy in treating T-cell-mediated inflammatory oral mucosal diseases, including lichen planus. However, the safety of topical tacrolimus has been questioned, based on its possible association with malignant transformation. Aim. To evaluate the safety aspects of tacrolimus in a three-dimensional in vitro model of oral mucosa containing both multilayered epithelium and connective tissue (raft culture). Methods. Raft cultures mimicking oral mucosa were topically exposed to tacrolimus, and the effects on cell proliferation and adhesion, epidermal growth factor receptors (EGFR, ERBB2, ERBB3, ERBB4), and apoptosis were evaluated with immunohistochemistry and terminal dUTP nick-end labelling, respectively. Results. The epithelium of the cultures was found to be slightly thinner, but no changes in cell proliferation or adhesion, apoptosis, or expression of epidermal growth factor receptors were detected. Conclusions. Our results suggest that short-term topical tacrolimus exposure of in vitro constructed oral mucosa does not induce changes in a number of factors known to be involved in malignant transformation.