Comparison of the anti‐apoptotic effects of Bcr‐Abl, Bcl‐2 and Bcl‐x<sub>L</sub> following diverse apoptogenic stimuli

Brumatti, Gabriela; Weinlich, Ricardo; Chehab, C. F.; Yon, Monica; Amarante-Mendes, Gustavo P.

doi:10.1016/s0014-5793(03)00299-0

Cited by 44 publications

(39 citation statements)

References 29 publications

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“…Recombinant Annexin V-FITC was produced as described earlier. 36 Isolation of adherent peritoneal cells. Four to six mice were injected intraperitoneally with 1 ml of thioglycolate (Sigma-Aldrich), and after 5 days, cells were obtained by peritoneal lavage with chilled RPMI-1640 medium.…”

Section: Methodsmentioning

confidence: 99%

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

et al. 2008

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Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms, including the expression of co-stimulatory molecules and the production of cytokines and other mediators that control T-cell proliferation, survival and differentiation. Here, we demonstrate that soluble factor(s) produced by Toll-like receptor (TLR)-activated APCs suppress activation-induced cell death (AICD). This effect was observed in non-stimulated APCs, but it was significantly increased after lipopolysaccharide (LPS) treatment. Using different KO mice, we found that the LPS-induced protective factor is dependent on TLR4/MyD88. We identified the protective factor as prostaglandin E 2 (PGE 2 ) and showed that both APC-derived supernatants and PGE 2 prevented CD95L upregulation in T cells in response to TCR/CD3 stimulation, thereby avoiding both AICD and activated T cell killing of target macrophages. The PGE 2 receptors, EP2 and EP4, appear to be involved since pharmacological stimulation of these receptors mimics the protective effect on T cells and their respective antagonists interfere with the protection induced by either APCs derived or synthetic PGE 2 . Finally, the engagement of EP2 and EP4 synergistically activates protein kinase A (PKA) and exchange protein directly activated by cAMP pathways to prevent AICD. Taken together, these results indicate that APCs can regulate T-cell levels of CD95L by releasing PGE 2 in response to LPS through a TLR4/MyD88-dependent pathway, with consequences for both T cell and their own survival. Cell Death and Differentiation (2008) 15, 1901-1909 doi:10.1038/cdd.2008 ; published online 26 September 2008Proper activation of T cells is imperative to achieve an efficient immunity against pathogens and tumors and, at the same time, to avoid undesirable collateral effects, such as the appearance of autoimmune diseases. Secondary lymphoid organs provide a particular microenvironment specialized in assembling all the cohorts necessary to perform such a remarkable task. 1 In the presence of antigens, antigenpresenting cells (APCs) and their soluble products, including a variety of cytokines, lipid mediators and chemokines, T cells are activated through the engagement of their T-cell receptors (TCR) and co-stimulatory molecules. As a result, T cells can proliferate, differentiate to effector or memory cells, or eventually die.Deletion of autoreactive T cells is one of the key mechanisms involved in the process of peripheral tolerance that helps to prevent the appearance of autoimmune diseases. 2 Similarly, elimination of chronically stimulated T cells that can potentially be harmful to the host by the means of the production of abnormal levels of inflammatory cytokines is another feature of an efficient immune system. Finally, death of effector T cells at the end of an immune response is a very important homeostatic mechanism designed to shrink an enlarged, no longer necessary cell population that can compete for growth and survival factors with newly activated antigen-specific T-cell clones. In a...

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Section: Methodsmentioning

confidence: 99%

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

et al. 2008

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“…Protein samples were resolved as previously described (33). Cells were harvested, washed in ice-cold PBS, lysed directly in SDS sample buffer (50 mM Tris-HCl [pH 6.8], 2% SDS, 10% glycerol, 2.5% 2-ME), and boiled for 5 min.…”

Section: Sds-page and Western Blotmentioning

confidence: 99%

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

Pedrosa

Weinlich

Mognol

et al. 2010

The Journal of Immunology

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“…Lymphocytes were labelled with annexin-V following the manufacturer's instructions (Brumatti et al 2003). Briefly, 10 6 cells were harvested at each point in time, washed twice with PBS and resuspended in a binding buffer containing annexin V-FITC (1:500).…”

Section: Analysis Of Cell Viability By Annexin-v and Pi Stainingmentioning

confidence: 99%

High susceptibility of activated lymphocytes to oxidative stress-induced cell death

Degasperi

Castilho

Vercesi

2008

An. Acad. Bras. Ciênc.

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The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca 2+ chelator BAPTA, the L-type Ca 2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca 2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.

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Comparison of the anti‐apoptotic effects of Bcr‐Abl, Bcl‐2 and Bcl‐x_L following diverse apoptogenic stimuli

Cited by 44 publications

References 29 publications

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

High susceptibility of activated lymphocytes to oxidative stress-induced cell death

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Comparison of the anti‐apoptotic effects of Bcr‐Abl, Bcl‐2 and Bcl‐xL following diverse apoptogenic stimuli

Cited by 44 publications

References 29 publications

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

TLR4/MYD88-dependent, LPS-induced synthesis of PGE2 by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

High susceptibility of activated lymphocytes to oxidative stress-induced cell death

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Comparison of the anti‐apoptotic effects of Bcr‐Abl, Bcl‐2 and Bcl‐x_L following diverse apoptogenic stimuli