A new defensive mechanism to prevent apoptosis in salivary ductal cells from patients with Sjögren's syndrome: over-expression of p53 and p21.

Abstract

In Sjögren's syndrome (SS), salivary acinar cells are destroyed even though ductal cells are frequently spared from destruction and can sometimes proliferate. We made the hypothesis that abnormalities of the tumour suppressor protein p53, either by mutations leading to proliferation or by activation of the functional wild-type p53, explain this phenomenon. Immunohistochemistry to detect p53 and its transcription target p21, which is expressed only if p53 is functional and not mutated, was performed on labial salivary glands (LSG) from 10 patients with primary SS, all of whom had a Chisholm grade 4 LSG biopsy, and from 10 control patients with sicca symptoms or systemic diseases and a normal LSG biopsy (grade 0 or 1). The p53 antigen could be detected in ductal cells of nine of 10 LSG from SS patients and only one of 10 LSG from controls. The p21 antigen was detected in ductal cells of eight of 10 LSG from SS patients and two of 10 LSG from controls. The p53 and p21 antigens were localized in the same ductal cells in SS patients, and the positive ducts were those located around lymphoid foci. The colocalization of p53 and its transcription factor p21 in salivary ductal cells surrounding lymphoid foci demonstrated that p53 was functional and not mutated. Its expression may be a defensive mechanism that provides ductal cells with time to repair DNA damage and prevents apoptosis. The lack of over-expression of p53 and p21 in acinar cells could be one of the key mechanisms of acinus destruction by apoptosis in SS and could be a target for new therapeutic strategies.