Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from patients infected with Shigella dysenteriae type 1 was studied by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and annexin V staining. Expression of proteins and cytokines participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL-18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute and convalescent stages of dysentery was quantified at the single-cell level by in situ immunostaining. Apoptotic cell death in the lamina propria was markedly up-regulated at the acute stage (P < 0.05), where an increased number of necrotic cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL-18, but not IL-2, at the acute stage than at the convalescent stage was observed. Increased expression of caspase-3 and IL-18 in tissues with severe inflammation compared to expression in those with mild inflammation was evident, implying a possible role in the perpetuation of inflammation. Significantly reduced cell death during convalescence was associated with a significant up-regulation of Bcl-2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of infection. Thus, induction of apoptosis at the local site in the early phase of S. dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival.
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PMID:Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2. 1201 Oct 15

Galectin-1, a beta-galactoside-binding protein expressed at sites of T-cell activation and immune privilege, has shown specific immunosuppressive properties. Because of the implications of this protein in T-cell tolerance and its potential use to avoid graft rejection, we investigated the immunosuppressive effects of galectin-1 in the course of the human allogenic T-cell response. Galectin-1 induced a dose- and carbohydrate-dependent inhibition of the allogenic T-cell response. Addition of galectin-1 to alloreactive lymphocytes resulted in significant apoptosis of CD45R0-positive cells. This negative regulatory effect was accompanied by caspase activation, Bcl-2 downregulation and was prevented by addition of exogenous IL-2. In addition, a significant decrease of IFN-gamma production was detected in the non-apoptotic cell population, following exposure of alloreactive lymphocytes to galectin-1. Moreover, the immunosuppressive activity of this protein did not involve TGF-beta-mediated mechanisms. Since galectin-1 is expressed by activated T cells and could be acting by an autocrine negative loop to control human T-cell reactivity, we finally examined the regulated expression of this protein throughout the allogenic T-cell response. Expression of endogenous galectin-1 was detected at 24 h of cell culture, reaching its maximal levels after 72 h of allostimulation. The present study sets the basis for a potential use of galectin-1 as a selective immunosuppressive agent to limit T-cell-mediated reactivity during the effector phase of the alloimmune response.
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PMID:Induction of allogenic T-cell hyporesponsiveness by galectin-1-mediated apoptotic and non-apoptotic mechanisms. 1203 75

Growth factor deprivation is a physiological mechanism to induce apoptosis. We used an IL-2-dependent murine T cell line to identify proteins that trigger apoptosis. Here we report the identification, the cloning and characterization of ITM2B(s), a protein induced upon IL-2-deprivation. ITM2B(s), which shares the BH3 domain of Bcl-2 family members, is a cytoplasmic and mitochondrial protein. Expression of ITM2B(s) induces apoptosis in IL-2-stimulated cells, but not in IL-4-stimulated cells, while overexpression of the long form of the protein is not able to induce apoptosis. In IL-2-stimulated cells, ITM2B(s) interacts with the antiapoptotic protein Bcl-2, and does not interact with the proapoptotic Bad. Mutation of the critical L and D residues within the BH3 domain abolished the ability of ITM2B(s) to promote apoptosis.
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PMID:Proapoptotic activity of ITM2B(s), a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2. 1208 33

T lymphocytes are heterogeneous with respect to their ability to proliferate following activation in vitro and in vivo. Approximately 30% of T lymphocytes fail to progress through the cell cycle, despite showing evidence of an activated state. The population of T lymphocytes that remains undivided during a primary stimulation has been shown to be refractory to restimulation via the TCR and fails to proliferate in response to IL-2. In an in vitro model of T-cell deletion following clonal expansion, we demonstrate that T lymphocytes that do not progress through the cell cycle during primary stimulation have a sevenfold greater survival advantage compared with T lymphocytes that have divided. Progression through multiple division cycles is associated with down-regulation of Bcl-2 during a postactivation period of growth factor withdrawal. However this alone does not account for diminished survival, as constitutive expression of a Bcl-2 transgene did not restore survival to the levels seen in undivided cells. Engagement of the IL-2 receptor on these undivided activated T lymphocytes leads to enhanced survival and up-regulation of Bcl-2 and Bcl-xL. Surprisingly, while IL-2 also induces phosphorylation of Akt, it does not initiate cell cycle progression in this population of primary undivided cells. Our data provide evidence that a T cell's survival capacity is linked to its proliferative behavior. Furthermore, our results provide the first report of a population of T cells, in which the IL-2 receptor-mediated signaling pathways leading to survival and proliferation are naturally uncoupled.
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PMID:Interleukin-2-mediated survival and proliferative signals are uncoupled in T lymphocytes that fail to divide after activation. 1209 13

Glutamine is the most abundant amino acid in the body. A decrease of plasma glutamine concentrations is found in catabolic stress and is related to susceptibility to infections. Glutamine is known to modulate lymphocyte activation; however, little is known about glutamine modulation of cell death of activated human T cells. Using Jurkat T cells, we investigated glutamine modulation of T-cell apoptosis activated by PMA plus ionomycin. We found that glutamine at various concentrations significantly enhanced IL-2 production, cell proliferation, and cell viability of Jurkat T cells. Glutamine also decreased the number of apoptotic cells stimulated with PMA plus ionomycin as demonstrated by flow cytometry. Meanwhile, glutamine down-regulated CD95 and CD95L expression, but up-regulated CD45RO and Bcl-2 expression in activated T cells. Further investigation of CD95-mediated caspase activities revealed that supplementation of glutamine significantly decreased caspase-3 and caspase-8 activities in activated T cells. Since oxidative stress is closely associated with induction of lymphocyte apoptosis, we found that glutamine significantly increased glutathione (GSH), but decreased reactive oxygen species levels in activated T cells. Blockade of intracellular GSH formation enhanced, but exogenous GSH supplementation decreased, activated T-cell apoptosis. Studying normal peripheral lymphoproliferation, we also found that the presence of glutamine increased lymphoproliferation as well as Bcl-2 and CD95 expression; but decreased CD95L and activation-induced T-cell death. Taken together, glutamine appeared to augment lymphoproliferation but suppressed activation-induced T-cell death in both Jurkat T cells and human peripheral T lymphocytes.
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PMID:Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. 1216 76

We report the case of a young female patient with chronic active Epstein-Barr virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB). She showed a marked increase of NK cell population in peripheral blood. The NK cell population was suggested to be infected with EBV, and to be oligoclonal by Southern blotting using an EBV genome terminal-repeat probe. The NK cells aberrantly expressed CD25, a high affinity receptor for IL-2, and showed an augmented in vitro proliferative response to IL-2. Moreover, they also showed enhanced expression of both Fas-ligand and Bcl-2, and resistance to in vitro Fas-induced apoptotic cell death (Fas-ACD). Taken together, these observations suggested that both the augmentation of proliferative response to IL-2 and the decrease in Fas-ACD may cause NK cell lineage granular lymphocyte proliferative disorder (NK-GLPD) in patients with CAEBV and SHMB.
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PMID:A possible mechanism of NK cell-lineage granular lymphocyte proliferative disorder (NK-GLPD) in a patient with chronic active Epstein-Barr virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB). 1221 36

Bag-1 exerts powerful antiapoptotic effects by binding and stabilizing Bcl-2 and interacting with the tumor necrosis factor receptor type I-induced death signal. We examined the effects of overexpression of Bag-1 by ex vivo adenoviral gene transfer on cold (4 degrees C for 24 hr) ischemia/reperfusion (I/R) injury of rat livers. Treatment with adenoviral Bag-1 (Ad-Bag-1) significantly improved portal venous blood flow, increased bile production, and improved hepatic function in the ex vivo model of cold ischemia followed by isolated perfusion. Moreover, the survival of orthotopic liver grafts subjected to cold ischemia increased from 50% in Ad-betaGal-treated controls to 100% after Ad-Bag-1 therapy. This effect correlated with preserved hepatic architecture, improved liver function, and depressed infiltration by neutrophils. Furthermore, the activation of infiltrating T cells, as measured by CD25, IL-2, and IFN-gamma mRNA expression was markedly reduced in the Ad-Bag-1 group. Hence, gene therapy-induced Bag-1 overexpression prevented cold I/R injury in rat livers. These findings provide the rationale for refined novel treatment of donor livers and may ultimately improve the overall success of liver transplantation.
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PMID:Upregulation of Bag-1 by ex vivo gene transfer protects rat livers from ischemia/reperfusion injury. 1221 70

Interactions between 4-1BB and its ligand, 4-1BBL, enhance CD8(+) T cell-mediated antiviral and antitumor immunity in vivo. However, mechanisms regulating the priming of CD8(+) T cell responses by 4-1BB remain unclear, particularly in humans. The 4-1BB receptor was undetectable on naive or resting human CD8(+) T cells and induced in vitro by TCR triggering. Naive cord blood cells were therefore primed in vitro against peptides or cellular antigens and then co-stimulated with 4-1BBL or agonistic antibodies. Co-stimulation enhanced effector function such as IFN-gamma production and cytotoxicity by augmenting numbers of antigen-specific and effector CD8(+) T cells. OKT3 responses also showed reduced cell death and revealed that the proliferation of CD8(+) T cells required two independently regulated events. One, the induction of IL-2 production, could be directly triggered by 4-1BB engagement on CD8(+) T cells in the absence of accessory cells. The other, expression of CD25, was induced with variable efficacy by accessory cells. Thus, suboptimal accessory cells and 4-1BB co-stimulation combined their effects to enhance IL-2 production and proliferation. Reduced apoptosis observed after co-stimulation in the presence of accessory cells correlated with increased levels of Bcl-X(L) in CD8(+) T cells, while Bcl-2 expression remained unchanged. Altogether, 4-1BB enhanced expansion, survival and effector functions of newly primed CD8(+) T cells, acting in part directly on these cells. As 4-1BB triggering could be protracted from the TCR signal, 4-1BB agonists may function through these mechanisms to enhance or rescue suboptimal immune responses.
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PMID:4-1BB co-stimulation enhances human CD8(+) T cell priming by augmenting the proliferation and survival of effector CD8(+) T cells. 1235 81

IL-2/IL-15Rbeta-deficient mice display impaired development of NK cells, NKT cells, and intraepithelial lymphocytes of the intestine and skin. To determine the role of survival signals mediated by IL-2/IL-15R in the development of these innate lymphocytes, we introduced a bcl-2 transgene into IL-2/IL-15Rbeta-deficient mice. Enforced expression of Bcl-2 restored the number of NK cells in IL-2/IL-15Rbeta-deficient mice, but the rescued NK cells showed no cytotoxic activity. The numbers of NKT cells and intestinal intraepithelial lymphocytes did not increase significantly, and skin intraepithelial lymphocytes remained undetectable in the bcl-2 transgenic IL-2/IL-15Rbeta-deficient mice. These results indicate an essential role of IL-2/IL-15R-mediated survival signals in the development of NK cells, but they also show that additional nonsurvival signals from IL-2/IL-15R are necessary for innate lymphocyte development.
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PMID:Enforced expression of Bcl-2 restores the number of NK cells, but does not rescue the impaired development of NKT cells or intraepithelial lymphocytes, in IL-2/IL-15 receptor beta-chain-deficient mice. 1237 Mar 44

The apoptosis phenomenon was identified approximately 40 years ago. In 1972, Kerr coined the term of apoptosis (programmed cellular death) to indicate that this way of cellular death was related to organic damage; but in contrast to other ways of death characterized by active cellular necrosis, in this, there is very little tissular reaction surrounding apoptotic cells. Apoptosis refers to the morphologic findings characterized by cellular shrink, nuclear condensation, fading of the membrane and fragmentation of this in apoptotic bodies with changes that possibly guide to the phagocytosis of the affected cell. Although there is great advance on phagocytosis mechanisms, signaling roads and pathology findings; a little is known about the molecular ways of apoptosis, intervening a great quantity of genes, surface receptors of T and B cells; ligand/receptor of death systems (particularly CD95), receptor of the tumoural necrosis factor (TNF-R), several interleukins with antiapoptotic activity, (specially IL-2), costimulatory receptors such as CD28 and proteins of the family Bcl-2 also with antiapoptotic activity. However, at this moment, the attention is focused in the apoptosis signaling pathways mediated by caspases, from which, 14 are known. Apoptosis has an important biological role in the development and homeostasis of cellular populations and in the pathogenesis and expression of diseases' processes. An excessive or insufficient apoptosis contributes to the pathogenesis of a wide variety of ischemic, neurodegenerative, and autoimmune diseases and viral infections, besides of participating in the growth and regression of tumoural processes. This article presents a general outline of the different apoptosis signaling pathways, the integration of multiple involved genes and receptors and the participation in several diseases of this programmed cellular death, either in excess or insufficient.
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PMID:[Apoptosis]. 1237 45


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