RESUMO
CD137 is a potent co-stimulatory molecule on activated T cells, and its ligand (CD137L) is expressed on antigen presenting cells (APC). Ectopic expression of CD137 has been identified on Hodgkin Reed-Sternberg (HRS) cells, the malignant cells in Hodgkin Lymphoma (HL), and CD137 on HRS cells was found to support growth of HRS cells and escape from immune surveillance. HRS cells are mostly derived from B cells, which poses the question of how B cells acquire ectopic CD137 expression during the transformation process. HL is associated with Epstein-Barr virus (EBV) infection. We show that the EBV latent membrane protein 1 (LMP1) induces expression of CD137 in HRS cell lines. In a HL tissue microarray, 96% of the CD137-positive HL cases stained positive for LMP1. LMP1 utilizes the PI3K-AKT-mTOR pathway for inducing CD137 expression. These findings support the role of EBV in HL pathogenesis.
Assuntos
Regulação Neoplásica da Expressão Gênica , Doença de Hodgkin/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Proteínas da Matriz Viral/metabolismo , Apoptose , Proliferação de Células , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Células de Reed-Sternberg , Serina-Treonina Quinases TOR/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Proteínas da Matriz Viral/genéticaRESUMO
Corticosteroids have been proved to be ineffective for Guillain-Barré syndrome, but the mechanism remains unknown. In a rabbit model of axonal Guillain-Barré syndrome, treatment with corticosteroids significantly reduced macrophage infiltration in the spinal ventral roots and the survival rate as well as clinical improvement. On 30(th) day after onset, there was significantly higher frequency of axonal degeneration in the corticosteroids-treated rabbits than saline-treated rabbits. Corticosteroids may reduce the scavengers that play a crucial role for nerve regeneration, thus delay the recovery of this disease.
