Production of reactive oxygen intermediates following CD40 ligation correlates with c-Jun N-terminal kinase activation and IL-6 secretion in murine B lymphocytes

Lee, Jong Ran; Koretzky, Gary A.

doi:10.1002/(sici)1521-4141(199812)28:12<4188::aid-immu4188>3.0.co;2-b

Cited by 82 publications

(71 citation statements)

References 48 publications

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“…On the basis of our data, we propose that CD40 stimulation sensitizes CLL cells to rituximab-mediated death by increasing basal ROS production, which is further increased by rituximab. ROS production after CD40 stimulation has been described before in B cells, 57 and CD40-induced ROS have critical roles in CD40-mediated B-cell regulation, for example, nuclear factor-kB signaling. 58 Our data indicate that constitutive CD40 signaling results in activation of CLL cells and increased basal ROS production.…”

Section: Discussionmentioning

confidence: 65%

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

et al. 2011

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In vitro CD40-stimulated chronic lymphocytic leukemia (CLL) cells are resistant to cytotoxic drugs. In sharp contrast, we here show that CD40 stimulation sensitizes CLL cells to rituximabmediated cell death. This increased sensitivity is specific for anti-CD20 treatment. Rituximab-mediated death in CD40-stimulated CLL cells shows rapid kinetics (within hours), and is caspase and p53 independent, but depends on extracellular Ca 2 þ and reactive oxygen species (ROS) production. By increasing basal ROS production, CD40 stimulation sensitizes CLL cells to rituximab-mediated death. Our findings provide a rationale for combination treatment of CLL with cytotoxic drugs and anti-CD20 monoclonal antibodies.

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Section: Discussionmentioning

confidence: 65%

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

et al. 2011

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“…Moreover, pharmacological inhibitors of JNK have been shown to confer protection from apoptosis in a human B cell line (39). In contrast, studies have shown that CD40-mediated signaling and treatment of B cells with CpG DNA, both of which exert potent anti-apoptotic effects, potently induce activation of JNK (55)(56)(57). However, it should be noted that activation of JNK under these conditions does not appear to be required for the protective effect of these pro-survival agonists (55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

The Adaptor Protein HSH2 Attenuates Apoptosis in Response to Ligation of the B Cell Antigen Receptor Complex on the B Lymphoma Cell Line, WEHI-231

Herrin

Groeger

Justement

2005

Journal of Biological Chemistry

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Signals transduced by the B cell antigen receptor (BCR) play a central role in regulating the functional response of the cell to antigen. Depending on the nature of the antigenic signal and the developmental or differentiation state of the B cell, antigen receptor signaling can promote either apoptosis or survival and activation. Understanding the molecular mechanisms underlying BCR-mediated apoptosis constitutes an important area of research because aberrations in programmed cell death can result in the development of autoimmunity or cancer. Expression of the adaptor protein hematopoietic Src homology 2 (HSH2) was found to significantly decrease BCR-mediated apoptosis in the murine WEHI-231 cell line. Analysis of signal transduction pathways activated in response to BCR ligation revealed that HSH2 does not significantly alter total protein tyrosine phosphorylation or Ca 2؉ mobilization. HSH2 does not potentiate the activation-dependent phosphorylation of AKT either. With respect to MAPK activation, HSH2 was not observed to alter the activation of ERK or p38 in response to BCR ligation, but it does significantly potentiate JNK activation. Analysis of processes directly associated with apoptosis revealed that HSH2 inhibits mitochondrial depolarization to a significant degree, whereas it has only a slight effect on caspase activation and poly ADP-ribose polymerase cleavage. BCR-induced apoptosis of WEHI-231 cells is associated with the loss of endogenous HSH2 expression within 12 h, whereas inhibition of apoptosis in response to CD40-mediated signaling leads to stabilization of HSH2 expression. Thus, endogenous HSH2 expression correlates directly with survival of WEHI-231 cells, which supports the hypothesis that HSH2 modulates the apoptotic response through its ability to directly or indirectly promote mitochondrial stability.

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“…Maintenance of the WEHI 231 mouse B lymphoma line and isolation of splenic B cells were described previously (11). When stimulated, the cells *Division of Molecular Life Sciences and Center for Cell Signaling Research, and † Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, Korea (WEHI 231: 5 ϫ 10 5 /ml, splenic B cells: 1 ϫ 10 6 /ml) were incubated with anti-CD40 mAb (R&D Systems, Minneapolis, MN) at 1 g/ml for indicated times.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…The cells were transfected with 40 g of the vector, or the indicated expression plasmid DNA, along with 5 g of the GFP plasmid for immunocytochemistry. Reporter gene assays were performed as described previously (11) and luminescence was determined using Luminoskan TL Plus (Bio-Orbit, Turku, Finland).…”

Section: Transient Transfections and Reporter Gene Assaymentioning

confidence: 99%

Cutting Edge: Induced Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, Following CD40 Stimulation and WEHI 231 B Cell Activation

Lee

Kim

2003

The Journal of Immunology

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Stimulation of the B cell surface receptor CD40 induces transcriptional activation and protein expression. To determine which proteins are required for the CD40-mediated B cell activation, we performed a two-dimensional gel electrophoresis of the WEHI 231 B cell lysates. We report in this study the identification of one protein in which the expression was remarkably induced following CD40 stimulation. It was the p190 Rho guanine nucleotide exchange factor (GEF), p190RhoGEF, a recently identified GEF that is specific for RhoA. Overexpression of either p190RhoGEF or RhoA (Q63L), a constitutively active form of RhoA, mimics the effects of CD40 stimulation, such as changes in cellular structure and NF-κB activation. These p190RhoGEF overexpression effects are abrogated when coexpressed with a dominant negative form of RhoA (T19N). We also provide evidence for the CD40-mediated cellular changes that are abrogated in cells that are overexpressed with the dominant negative form of either p190RhoGEF (Y1003A) or RhoA (T19N).

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Production of reactive oxygen intermediates following CD40 ligation correlates with c-Jun N-terminal kinase activation and IL-6 secretion in murine B lymphocytes

Cited by 82 publications

References 48 publications

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

The Adaptor Protein HSH2 Attenuates Apoptosis in Response to Ligation of the B Cell Antigen Receptor Complex on the B Lymphoma Cell Line, WEHI-231

Cutting Edge: Induced Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, Following CD40 Stimulation and WEHI 231 B Cell Activation

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