title: 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 Sjogren'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-1beta, TGF-beta1, or IL-10. However, XIAP expression was down-regulated by TNF-alpha, which induced apoptotic cell death of HSG cells with an increase in caspase-3 activity. These effects of TNF-alpha in HSG cells were antagonized by IL-1beta, TGF-beta1, 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.
authors.affiliation: First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Kamachi
authors.forename: K
authors.initials: K
authors.lastname: Migita
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Koji
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011506:Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012469:Salivary Glands / Q000737:chemistry; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051636:X-Linked Inhibitor of Apoptosis Protein; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051020:bcl-X Protein