Expression and function of X chromosome-linked inhibitor of apoptosis protein in Sjogren's syndrome

Apoptotic cell death in acinar and ductal epithelial cells is thought to pl ay an important role in the development of salivary gland dysfunction in pa tients with Sjogren's syndrome (SS). We examined the expression of anti-apo ptotic molecules in salivary glands from patients with SS. The labial saliv ary glands from six human T-cell leukemia Virus (HTLV)-/-seronegative and e leven HTLV-l-seropositive SS patients were analyzed by immunohistochemistry . In vitro experiments were performed with a human salivary gland cell line (HSG cells). Immunohistologic analyses revealed that Bcl-2 and Bcl-x were preferentially expressed in salivary infiltrating mononuclear cells more th an acinar and ductal epithelial cells. In contrast, strong X chromosome-lin ked inhibitor of apoptosis protein (XIAP) expression was evident in both ac inar and ductal epithelial cells. The pattern of expression of these anti-a poptotic molecules was similar in both HTLV-I-seropositive and HTLV-I -sero negative SS patients. Western blot analysis confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG cells was increased by I L-1 beta, TGF-beta 1, or IL-10. However, XIAP expression was down-regulated by INF-alpha, which induced apoptotic cell death of HSG cells with an incr ease in caspase-3 activity. These effects of TNF-alpha in HSG cells were an tagonized by IL-1 beta, TGF-beta 1, or IL-10. Our results suggest that XIAP is important in regulating apoptotic cell death of acinar and ductal epith elial cells in patients with SS.