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Exp Cell Res ; 398(1): 112399, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33245890

RESUMO

The development of Sjögren's syndrome (SS) is accompanied by B cell hyperproliferation and mutation. Our previous study identified aberrant expression of BST-2 (also known as Tetherin/CD317) in B cells from either the peripheral blood or infiltrated salivary glands. However, the roles of BST-2 in the regulation of B cell activation remain unknown. In this study, we identified that BST-2 can respond to BAFF simulation but not to other B cell simulators in neoplastic B cell lines. A CCK-8 assay, an EdU assay and Annexin V/PI staining indicated that BST-2 inhibition attenuated BAFF-enhanced proliferation and survival in both Raji cells and Daudi cells. Screening of BAFF-related signaling in neoplastic B-lymphoid cells indicated that BST-2 was involved in the regulation of NF-κB signaling upon BAFF simulation. However, inhibition of NF-κB by JSH-23 significantly reduced the proliferation and survival of Raji and Daudi cells under both normal and BAFF-simulated conditions. Collectively, our results indicate that BST-2/Tetherin is a BAFF-responsive membrane factor involved in the regulation of NF-κB signaling, thereby assisting in the proliferation and survival of neoplastic B-lymphoid cells. Our study provides a potential molecular mechanism underlying aberrant overactivation of B cells upon SS development.


Assuntos
Antígenos CD/metabolismo , Fator Ativador de Células B/metabolismo , Linfócitos B/metabolismo , Glicoproteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Animais , Linfócitos B/patologia , Proliferação de Células , Sobrevivência Celular , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos ICR , Camundongos Endogâmicos NOD , Transdução de Sinais , Células Tumorais Cultivadas
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