IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability and survival by activating Erk1/2 and S6K1 pathways in neoplastic B-lymphoid cells. (August 2016)

• Record Type: Journal Article
• Authors: Gui, Lin; Zeng, Qingyu; Xu, Zhigang; Zhang, Hai; Qin, Shanshan; Liu, Chunxiao; Xu, Chong; Qian, Zhou; Zhang, Shuangquan; Huang, Shile; Chen, Long
• Is Part Of: Cytokine. Volume 84(2016)
• Page Start: 37
• Page End: 46
• Publication Date: 2016-08
• Subjects: Cytokine -- BAFF -- B cell -- Erk1/2 -- S6K1; 4E-BP1 eukaryotic initiation factor 4E binding protein 1 -- Akt protein kinase B (PKB) -- BAFF B-cell activating factor of the TNF family -- BLyS B lymphocyte stimulator -- BCMA B cell maturation antigen -- Erk1/2 extracellular signal-related kinase 1/2 -- IFN interferon -- IL interleukin -- MAPK mitogen-activated protein kinase -- MKK mitogen-activated protein kinase kinase -- mTOR mammalian target of rapamycin -- PI3K phosphatidylinositol 3′-kinase -- RA rheumatoid arthritis -- S6K1 S6 kinase 1 -- SLE systemic lupus erythematosus -- SS Sjögren's syndrome -- TACI transmembrane activator and cyclophilin ligand interactor -- TALL-1 TNF and apoptosis ligand-related leukocyte-expressed ligand 1 -- THANK TNF homologue that activates apoptosis, nuclear factor κB and c-Jun NH2-terminal kinase; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.05.017
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-2/IL-4/IFN-γ/TNF-α reinforces BAFF-stimulated viability/survival in neoplastic B-lymphoid cells. IL-2/IL-4/IFN-γ/TNF-α enhances BAFF-stimulated B-cell viability/survival by activating Erk1/2 and S6K1 pathways. Manipulating IL-2/IL-4/IFN-γ/TNF-α level or blocking Erk1/2 or S6K1 may prevent BAFF-induced B-cell malignancies. Abstract: B-cell activating factor of the TNF family (BAFF) has been documented to act as a critical factor in the development of aggressive B lymphocytes and autoimmune diseases. However, the effect of various cytokines on BAFF-elicited neoplastic B-lymphoid cells is not known. In this study, we exhibited that administration of human soluble BAFF (hsBAFF), IL-2, IL-4, IFN-γ, or TNF-α alone increased cell viability and survival in Raji cells concentration-dependently, yet a more robust viability/survival was seen in the cells co-treatment of IL-2, IL-4, IFN-γ, or TNF-α with hsBAFF, respectively. Further research revealed that both Erk1/2 and S6K1 signaling pathways were essential for IL-2, IL-4, IFN-γ, or TNF-α enhancement of the viability/survival in the hsBAFF-stimulated cells, as inhibition of Erk1/2 with U0126 or down-regulation of Erk1/2, or blockage of S6K1 with rapamycin or silencing S6K1, or silencing S6K1/Erk1/2, respectively, reduced the cell viability/survival in the cells treated with/without hsBAFF ± IL-2, IL-4, IFN-γ, or TNF-α. These findings indicate that IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability/survival by activating Erk1/2 and S6K1 signaling in neoplastic B-lymphoid cells. Our data suggest that modulation of IL-2, IL-4, IFN-γ and/or TNF-α levels, or inhibitors of Erk1/2 or S6K1 may be a new approach to prevent BAFF-induced aggressive B-cell malignancies.