IFN-γ Induces the Apoptosis of WEHI 279 and Normal Pre-B Cell Lines by Expressing Direct Inhibitor of Apoptosis Protein Binding Protein with Low pI

Yoshikawa, Hideshi; Nakajima, Yasuo; Tasaka, Kachio

doi:10.4049/jimmunol.167.5.2487

Cited by 22 publications

(12 citation statements)

References 48 publications

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“…TGF␤-mediated apoptosis of Ramos cells has been associated with the down-regulation of Bcl-x L expression (28). In addition, studies have shown that IFN-␥ also induces the apoptosis of the immature B cell line WEHI 279 and normal murine pre-B cells via the downregulation of Bcl-2 and Bcl-x L (29). Although the receptors and ensuing signaling cascades for these cytokines are very different, the modulation of Bcl-2 family members appears to be an important common mechanism in determining cell survival.…”

Section: Discussionmentioning

confidence: 99%

IL-21 Induces the Apoptosis of Resting and Activated Primary B Cells

Mehta

Wurster

Whitters³

et al. 2003

The Journal of Immunology

183

175

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Cytokines play an important role in regulating the development and homeostasis of B cells by controlling their viability. In this study, we show that the recently described T cell-derived cytokine IL-21 induces the apoptosis of resting primary murine B cells. In addition, the activation of primary B cells with IL-4, LPS, or anti-CD40 Ab does not prevent IL-21-mediated apoptosis. The induction of apoptosis by IL-21 correlates with a down-regulation in the expression of Bcl-2 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Furthermore, the reconstitution of Bcl-xL or Bcl-2 expression protects primary B cells from IL-21-induced apoptosis. In addition, a short-term preactivation of B cells with anti-CD40 Ab confers protection from IL-21-mediated apoptosis through the up-regulation of Bcl-xL. These studies reveal a novel pathway that mediates B cell apoptosis via the IL-21R and suggest that IL-21 may play a role in regulating B cell homeostasis.

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Section: Discussionmentioning

confidence: 99%

IL-21 Induces the Apoptosis of Resting and Activated Primary B Cells

Mehta

Wurster

Whitters³

et al. 2003

The Journal of Immunology

183

175

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“…However, studies using cell lines suggest that Smac/DIABLO is important in the negative regulation of B-cell differentiation. IFN-γ, a factor that sensitizes apoptosis induces de novo synthesis of Smac/DIABLO and its release in the cytosol [131]. This sensitization of apoptosis by Smac/DIABLO has been exploited in experimental therapeutic models.…”

Section: Smac/diablo and Omi/htra2 Propagators Of Caspase-dependent mentioning

confidence: 99%

Bcl-2 Family Members as Sentinels of Cellular Integrity and Role of Mitochondrial Intermembrane Space Proteins in Apoptotic Cell Death

Festjens¹,

Gurp²,

Loo³

et al. 2003

Acta Haematol

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In addition to their function as major energy-providing organelles of the cell, mitochondria accomplish a crucial role in apoptosis. The pro-apoptotic BH3-only members of the Bcl-2 family continuously sense the cellular integrity and well-being at various subcellular levels. If these sentinels are induced, released or activated, they converge on the release of mitochondrial intermembrane space proteins such as cytochrome c, the oxidoreductase AIF, endonuclease G, Smac/DIABLO and the serine protease Omi/HtrA2. We discuss how Bcl-2 family members integrate diverse survival and death signals and act as central regulators of apoptosis. Furthermore, we describe the current knowledge on the role of mitochondrial proteins in apoptotic cell death, discuss the molecular mechanisms of their release and the apoptotic role of mitochondria from a phylogenetic and immunological point of view.

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“…These findings suggest that the prolonged survival of mast cells at inflammatory sites has advantages in fighting against bacterial infections. IFN-+ plays an important role in the activation of macrophages or cellular immunity, but negatively regulates allergic inflammation or humoral immunity [45], in which Th2 cytokines are dominantly produced by T cells and mast cells in sharp contrast to innate immunity. We also demonstrated that IFN-+ up-regulated the expression of TLR4 on mast cells and enhanced the stimulation by LPS, suggesting important roles for Th1 and inflammatory cytokines even in the activation of mast cells in innate immunity.…”

Section: Discussionmentioning

confidence: 99%

Caspase‐dependent and ‐independent apoptosis of mast cells induced by withdrawal of IL‐3 is prevented by Toll‐like receptor 4‐mediated lipopolysaccharide stimulation

Yoshikawa

Tasaka

2003

Eur J Immunol

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IL-3-dependent mucosal-like mast cells undergo apoptosis upon withdrawal of IL-3. Generally, the apoptosis is mediated by the activation of caspases and inhibited by addition of the pan-caspase inhibitors z-VAD-FMK or BOC-D-FMK. However, DNA fragmentation, a typical characteristic of apoptosis, is not inhibited by z-VAD-FMK or BOC-D-FMK in mast cell apoptosis. In this study, we demonstrate that the apoptosis of mast cells is mediated by both caspase-dependent and -independent mechanisms. The caspase-independent apoptosis is mediated by the translocation of endonuclease G from mitochondria into nuclei. Withdrawal of IL-3 caused down-regulation of Bcl-xL, resulting in a drop in mitochondrial membrane transition potential followed by the release of cytochrome c and endonuclease G from mitochondria. However, stimulation of mast cells through Toll-like receptor 4 (TLR4) by lipopolysaccharide prevented mast cell apoptosis by inducing expression of Bcl-xL. Moreover, the activation of mast cells by LPS is enhanced in the presence of IFN-+ , which up-regulates the expression of cell surface TLR4. Taken together, these observations provide evidence that mast cells play important roles not only in allergic reactions but also in innate immunity recognizing enterobacteria through TLR4, and are regulated differently from allergic inflammation by Th1 cytokines.

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IFN-γ Induces the Apoptosis of WEHI 279 and Normal Pre-B Cell Lines by Expressing Direct Inhibitor of Apoptosis Protein Binding Protein with Low pI

Cited by 22 publications

References 48 publications

IL-21 Induces the Apoptosis of Resting and Activated Primary B Cells

IL-21 Induces the Apoptosis of Resting and Activated Primary B Cells

Bcl-2 Family Members as Sentinels of Cellular Integrity and Role of Mitochondrial Intermembrane Space Proteins in Apoptotic Cell Death

Caspase‐dependent and ‐independent apoptosis of mast cells induced by withdrawal of IL‐3 is prevented by Toll‐like receptor 4‐mediated lipopolysaccharide stimulation

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