Expression and Function of X Chromosome-Linked Inhibitor of Apoptosis Protein in Sjögren's Syndrome

Abstract

Apoptotic cell death in acinar and ductal epithelial cells is thought to play an important role in the development of salivary gland dysfunction in patients with Sjögren's syndrome (SS). We examined the expression of anti-apoptotic molecules in salivary glands from patients with SS. The labial salivary glands from six human T-cell leukemia virus (HTLV)–I–seronegative and eleven HTLV-I–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 than acinar and ductal epithelial cells. In contrast, strong X chromosome-linked inhibitor of apoptosis protein (XIAP) expression was evident in both acinar and ductal epithelial cells. The pattern of expression of these anti-apoptotic molecules was similar in both HTLV-I–seropositive and HTLV-I–seronegative SS patients. Western blot analysis confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG cells was increased by IL-1β, TGF-β1, or IL-10. However, XIAP expression was down-regulated by TNF-α, which induced apoptotic cell death of HSG cells with an increase in caspase-3 activity. These effects of TNF-α in HSG cells were antagonized by IL-1β, TGF-β1, or IL-10. Our results suggest that XIAP is important in regulating apoptotic cell death of acinar and ductal epithelial cells in patients with SS.