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

Gui, Lin; Zeng, Qingyu; Xu, Zhigang; Zhang, Hai; Qin, Shanshan; Liu, Chunxiao; Xu, Chong; Zhou, Qian; Zhang, Shuangquan; Huang, Shile; Long, Chen

doi:10.1016/j.cyto.2016.05.017

Cited by 18 publications

(13 citation statements)

References 52 publications

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“…We speculate that the elevated BAFF, APRIL, BAFF-R, TACI, and BCMA expressions in the lymphoid tissues reflect activation at the site of antibody production. The determination of these parameters to indicate occurrence of the BAFF/APRIL system activation was consistent with the previous studies in animal malaria 38,39 and other human or animal diseases 3,21,26,27,41,42 and cell cultures 3,43 .…”

Section: Discussionsupporting

confidence: 89%

The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients

Dechkhajorn

Benjathummarak

Glaharn

et al. 2020

Sci Rep

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previous studies have reported activation of the B cell-activating factor (BAff)/a proliferation-inducing ligand (ApRiL) system in t independent immunity against malaria infection. Plasmodium falciparum (P. falciparum) infected animal model is not feasible. therefore, little is known about the occurrence of BAff/ApRiL system and changes in falciparum lymphoid tissues. this study aimed to investigate the expression of BAff/ApRiL system components in lymphoid tissues from P. falciparum infected patients. Spleen and lymph node samples from 14 patients were collected at autopsy. Normal spleens and bacterially infected tonsils served as controls. the protein and/or mRnA expression of BAff/ApRiL and their cognate receptors, BAff-R, tAci and BcMA, were determined by immunohistochemistry and Rt-qPCR, respectively. The spleens of the patients exhibited significantly higher BAFF-R protein expression than normal spleens. Although without appropriate control, BcMA protein was markedly observed only in the lymph nodes. BAFF and BCMA mRNA levels were also significantly elevated in the spleen tissues of the patients compared with normal spleens. the overall BAff-R protein levels in the lymphoid tissues of the patients correlated positively with parasitaemia. These findings are the first to confirm that BAFF/ ApRiL system activation in lymphoid tissues and is positively correlated with the parasitaemia levels in falciparum malaria. The B cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system consists of BAFF, APRIL, and three cognate receptors expressed on B cells: B cell maturation antigen (BCMA), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) 1 , and BAFF receptor (BAFF-R) 2-4. The BAFF/ APRIL system plays multiple regulatory roles in the T cell independent (TI) immune response, including B cell activation, homeostasis, and survival 5. APRIL binds with high affinity to both BCMA and TACI, while BAFF has lower affinity for these receptors and binds mainly to BAFF-R (reviewed in Dillon et al. 6). Ligand binding triggers activation of diverse signalling pathways, including the mitogen-activated kinase and nuclear factor-κB pathways 7,8 to induced immunoglobulin heavy chain class-switch recombination (CSR), and IgG and IgA production by B cells 5. BAFF and APRIL are predominantly expressed by myeloid cells such as monocytes, macrophages, and dendritic cells 9 and can be induced or upregulated by cytokines such as interferon-α and-γ, transforming growth factor-β, interleukin-4 and −10 2,10,11. Spleen and lymph nodes play pivotal roles in the host response to malaria. For example, the spleen eliminates Plasmodium parasitised red blood cells (PRBCs), and immune cells in both organs produce effector cytokines and specific anti-malaria antibodies that promote clearance of infection 12,13. The BAFF/APRIL system plays well-characterised roles in numerous human disorders, including autoimmune diseases 14-19 , cancers 20 , and bacterial 21 , viral 22 , and fungal 23 infections. ...

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Section: Discussionsupporting

confidence: 89%

The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients

Dechkhajorn

Benjathummarak

Glaharn

et al. 2020

Sci Rep

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“…During the onset and progression of OA, the concentration of TNF-α in the synovial fluid has been reported to increase, resulting in the induction of inflammation, promotion of the release of bone matrix-degrading enzymes, and the enhancement of fibroblastic hyperplasia and histological damage ( 6 ). The Ras-Raf-mitogen-activated protein kinase kinase (MEK)1/2-extracellular signal-regulated kinase (ERK)1/2 signaling pathway regulates the TNF-α-induced inflammatory response, and finally leads to cartilage degradation ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture serum inhibits TNF-α-mediated chondrocyte inflammation via the Ras-Raf-MEK1/2-ERK1/2 signaling pathway

Chen¹,

Shao²,

Li³

et al. 2017

Molecular Medicine Reports

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The Ras-Raf-mitogen-activated protein kinase kinase (MEK)1/2-extracellular signal-regulated kinase (ERK)1/2 signaling pathway contributes to the release of chondral matrix-degrading enzymes and accelerates the degradation of articular cartilage. Electroacupuncture (EA) treatment has been widely used for the treatment of osteoarthritis (OA); however, the mechanism underlying the effects of EA on OA remains unclear. Therefore, the present study evaluated the anti-inflammatory effects and potential underlying mechanisms of EA serum (EAS) on tumor necrosis factor (TNF)-α-mediated chondrocyte inflammation. A total of 30 Sprague Dawley rats were randomly divided into three groups: The blank group; experimental group I, which received 15 min of EA treatment; and experimental group II, which received 30 min of EA treatment. Subsequently, serum samples were obtained. Chondrocytes were isolated from the knee cartilage of Sprague Dawley rats, and were identified using collagen type II immunohistochemistry. TNF-α-treated chondrocytes were used as a cell model, and subsequently the cells were treated with EAS from each group for various durations. The results demonstrated that EAS treatment significantly promoted the viability and inhibited the apoptosis of TNF-α-treated chondrocytes. In addition, interleukin (IL)-1β concentration was significantly increased in the model group compared with in the control group, whereas EAS significantly reduced IL-1β concentration in TNF-α-treated chondrocytes. Furthermore, the protein expression levels of Ras, Raf and MEK1/2 were reduced in the EAS groups compared with in the model group. EAS also significantly inhibited the phosphorylation of ERK1/2, and the expression of downstream regulators matrix metalloproteinase (MMP)-3 and MMP-13. In conclusion, these results indicated that EAS may inhibit TNF-α-mediated chondrocyte inflammation via the Ras-Raf-MEK1/2-ERK1/2 signaling pathway in vitro, thus suggesting that EAS may be considered a potential therapeutic strategy for the treatment of OA.

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“…These cytokines have pro-proliferation and antiapoptotic effects in a variety of cells, including B cells. IL-2 extensively participates in immune response, including the proliferation/viability, survival, and immunoglobulin secretion in normal and neoplastic B-lymphoid cells (60). For instance, IL-2 evokes proliferation of activated B cells by binding to the surface receptors and induces human plasma cell differentiation (61), and it acts as a pro-survival factor in B-cell chronic lymphocytic leukemia (B-CLL) to prevent the leukemic cells from undergoing apoptosis (62).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of MicroRNA 711 Mediates HIV-1 Vpr Promotion of Kaposi's Sarcoma-Associated Herpesvirus Latency and Induction of Pro-proliferation and Pro-survival Cytokines by Targeting the Notch/NF-κB-Signaling Axis

Yan

Zhao

Shen

et al. 2018

J Virol

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Coinfection with HIV-1 and Kaposi's sarcoma-associated herpesvirus (KSHV) often leads to AIDS-related malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). The interaction between HIV and KSHV plays a pivotal role in the progression of these malignancies. We have previously demonstrated that, by upregulating miR-942-5p, HIV-1 viral protein R (Vpr) inhibits KSHV lytic replication by targeting IκBα to activate the NF-κB signaling (Q. Yan, C. Shen, J. Qin, W. Li, M. Hu, H. Lu, D. Qin, J. Zhu, S. J. Gao, C. Lu, J Virol 90:8739-8753, 2016). Here, we show that Vpr inactivates Notch signaling, resulting in inhibition of KSHV lytic replication and induction of pro-proliferative and -survival cytokines, including interleukin-2 (IL-2), TIMP-1, IGF-1, and NT-4. Mechanistically, Vpr upregulates miR-711, which directly targets the Notch1 3' untranslated region. Suppression of miR-711 relieved Notch1 and reduced Vpr inhibition of KSHV lytic replication and Vpr induction of pro-proliferation and -survival cytokines, while overexpression of miR-711 exhibited the opposite effect. Finally, overexpression of Notch1 reduced Vpr induction of NF-κB activity by promoting IκBα promoter activity. Our novel findings reveal that by upregulating miR-711 to target Notch1, Vpr silences Notch signaling to activate the NF-κB pathway by reducing IκBα expression, leading to inhibition of KSHV lytic replication and induction of pro-proliferation and -survival cytokines. Therefore, the miR-711/Notch/NF-κB axis is important in the pathogenesis of AIDS-related malignancies and could be an attractive therapeutic target. HIV-1 infection significantly increases the risk of KS and PEL in KSHV-infected individuals. Our previous study has shown that HIV-1 Vpr regulates the KSHV life cycle by targeting IκBα to activate NF-κB signaling through upregulating cellular miR-942-5p. In this study, we have further found that Vpr inactivates Notch signaling to promote KSHV latency and production of pro-proliferation and -survival cytokines. Another Vpr-upregulated cellular microRNA, miR-711, participates in this process by directly targeting Notch1. As a result, Notch1 upregulation of the IκBα promoter activity is attenuated, resulting in reduced levels of IκBα transcript and protein. Overall, these results illustrate an alternative mechanism of HIV-1 Vpr regulation of KSHV latency and aberrant cytokines through the miR-711/Notch/NF-κB axis. Our novel findings further demonstrate the role of an HIV-1-secreted regulatory protein in the KSHV life cycle and KSHV-related malignancies.

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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

Cited by 18 publications

References 52 publications

The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients

The activation of BAFF/APRIL system in spleen and lymph nodes of Plasmodium falciparum infected patients

Electroacupuncture serum inhibits TNF-α-mediated chondrocyte inflammation via the Ras-Raf-MEK1/2-ERK1/2 signaling pathway

Upregulation of MicroRNA 711 Mediates HIV-1 Vpr Promotion of Kaposi's Sarcoma-Associated Herpesvirus Latency and Induction of Pro-proliferation and Pro-survival Cytokines by Targeting the Notch/NF-κB-Signaling Axis

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