Epidermal Growth Factor Receptor involvement in Behcet's Disease oral ulceration

Behcet's Disease (BD) is a multi-systemic inflammatory disorder whose major feature is chronic oral ulceration with slow healing and atrophic scarring. Previously, we reported that salivary epidermal growth factor (EGF) was significantly high in BD patients and that BD buccal epithelial cells were not able to utilize EGF present in culture medium. We hypothesized that EGF receptor (EGFR) was deficient in BD epithelial cells which could explain the delay in mucosal wound healing in BD patients. Objectives: To investigate EGF and EGFR mRNA and protein expression in the buccal epithelial cells of BD patients and healthy controls. Methods: Buccal swabs from BD patients (N=23) and healthy controls (HC) (N=7) were obtained by brushing the inside of the cheek with a sterile nylon bristle cytology brush. RNA was extracted and reverse transcribed to cDNA. Gene expression of EGF and EGFR was measured by real time PCR and expression of EGFR was analysed by Western Blotting using proteins precipitated from swabs. Results: Real-Time PCR showed no expression of EGF in buccal epithelial cells in both HC and BD groups. EGF previously reported in saliva must therefore originate from the salivary glands. Real Time PCR and Western blotting demonstrated that EGFR gene and protein expression in BD patients were lower than in healthy controls. Conclusion: EGF is important in oral wound healing and reduction in EGF-R has been shown in chronic dermal ulcers and diabetic foot ulcers. In our study, the buccal epithelium of BD patients expresses less EGF-R and this could explain the delayed healing of mouth ulcers. Further work will investigate EGF-EGFR downstream signaling and the regulation of EGFR expression after microbial challenge. Human cytomegalovirus (HCMV) infection has been implicated in BD and has also been shown to down regulate EGFR in lung by retarding its maturation and innate immunity.