OBJECTIVES: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren's syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C-delta (PKCδ) is known to play a critical role in B-cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B-cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ-/- mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. MATERIALS AND METHODS: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. RESULTS: PKCδ-/- mice have reduced salivary gland function, B220+ B-cell infiltration, anti-nuclear antibody production, and elevated IFN-γ in the salivary glands as compared to PKCδ+/+ littermates. CONCLUSIONS: PKCδ-/- mice have exocrine gland tissue damage indicative of a SS-like phenotype.
OBJECTIVES: Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren's syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C-delta (PKCδ) is known to play a critical role in B-cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B-cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ-/- mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined. MATERIALS AND METHODS: Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages. RESULTS:PKCδ-/- mice have reduced salivary gland function, B220+ B-cell infiltration, anti-nuclear antibody production, and elevated IFN-γ in the salivary glands as compared to PKCδ+/+ littermates. CONCLUSIONS:PKCδ-/- mice have exocrine gland tissue damage indicative of a SS-like phenotype.
Authors: Stina Salomonsson; Malin V Jonsson; Kathrine Skarstein; Karl A Brokstad; Peter Hjelmström; Marie Wahren-Herlenius; Roland Jonsson Journal: Arthritis Rheum Date: 2003-11
Authors: Joanna Groom; Susan L Kalled; Anne H Cutler; Carl Olson; Stephen A Woodcock; Pascal Schneider; Jurg Tschopp; Teresa G Cachero; Marcel Batten; Julie Wheway; Davide Mauri; Dana Cavill; Tom P Gordon; Charles R Mackay; Fabienne Mackay Journal: J Clin Invest Date: 2002-01 Impact factor: 14.808
Authors: Arne Hansen; Marcus Odendahl; Karin Reiter; Annett M Jacobi; Eugen Feist; Jürgen Scholze; Gerd R Burmester; Peter E Lipsky; Thomas Dörner Journal: Arthritis Rheum Date: 2002-08
Authors: Ingrid Mecklenbräuker; Susan L Kalled; Michael Leitges; Fabienne Mackay; Alexander Tarakhovsky Journal: Nature Date: 2004-09-08 Impact factor: 49.962
Authors: S D Khare; I Sarosi; X Z Xia; S McCabe; K Miner; I Solovyev; N Hawkins; M Kelley; D Chang; G Van; L Ross; J Delaney; L Wang; D Lacey; W J Boyle; H Hsu Journal: Proc Natl Acad Sci U S A Date: 2000-03-28 Impact factor: 11.205