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)

Eosinophils are potent inflammatory cells involved in allergic reactions. Inhibition of apoptosis of purified eosinophils by certain cytokines has been previously shown to be an important mechanism causing tissue eosinophilia. To elucidate the role of Bcl-2 family members in the inhibition of eosinophil apoptosis, we examined the expression of the known anti-apoptotic genes Bcl-2, Bcl-xL, and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human eosinophils express significant amounts of Bcl-xL and Bax, but only little or no Bcl-2, Bcl-xS, or A1. As assessed by reverse transcription-polymerase chain reaction, immunoblotting, flow cytometry, and immunocytochemistry, we show that spontaneous eosinophil apoptosis is associated with a decrease in Bcl-xL mRNA and protein levels. In contrast, stimulation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-5 (IL-5) results in maintenance or upregulation of Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is also not expressed in tissue eosinophils as assessed by immunohistochemistry using two different eosinophilic tissue models. Furthermore, Bcl-xL antisense but not scrambled phosphorothioate oligodeoxynucleotides can partially block the cytokine-mediated rescue of apoptotic death in these cells. These data suggest that Bcl-xL acts as an anti-apoptotic molecule in eosinophils.
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PMID:Role for Bcl-xL in delayed eosinophil apoptosis mediated by granulocyte-macrophage colony-stimulating factor and interleukin-5. 968 Mar 44

The in situ apoptosis and the expression of molecules involved in this process, such as Bcl-2, Fas, and its ligand, Fas ligand (FasL), were examined in bronchial biopsies from healthy control subjects and from steroid-untreated or -treated asthmatics, using terminal transferase-mediated deoxyuridyltriphosphate nick-end labeling and immunohistochemical techniques, respectively. Bronchial submucosa from steroid- untreated asthmatics showed an increase in the number of eosinophils and a decrease in that of apoptotic cells compared with that of control subjects, but no significant changes in the number of T lymphocytes or in that of cells expressing Bcl-2, Fas, or FasL. Treatment with steroids reduced airway eosinophilia and augmented the proportion of apoptotic eosinophils. Compared with control subjects or untreated patients, steroid-treated asthmatics exhibited increased expression of Bcl-2, Fas, FasL, and of proliferating cell nuclear antigen (PCNA) in their bronchial epithelium, without changes in the number of apoptotic cells. Moreover, the intensity of the expression of Bcl-2, Fas, and FasL correlates well with that of PCNA. We conclude that steroids may reduce the inflammatory cell infiltrate in the bronchial submucosa in part by promoting eosinophil apoptosis and by inducing the expression of FasL on bronchial epithelial cells. Treatment with steroids may also augment survival and proliferation of epithelial cells, possibly via the expression of Bcl-2 and PCNA.
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PMID:Apoptosis, proliferation, and expression of Bcl-2, Fas, and Fas ligand in bronchial biopsies from asthmatics. 980 39

Semliki Forest virus (SFV) infection of mice is used as a model to study pathogenic processes occurring in viral encephalitis. It has previously been shown that avirulent strains of SFV differ from virulent strains in showing restricted multiplication in neurones and in producing localized rather than widespread lesions in the central nervous system (CNS). Restricted neuronal damage is age-dependent and does not occur in neonatal animals. In this study, cell death mechanisms occurring in the CNS of adult rats infected intranasally (i.n.) with a virulent (SFV4) and an avirulent (A7) strain of SFV have been investigated. Although i.n. infection of rats was less efficient than that of mice, SFV4 reached a higher titre in the CNS of infected animals than A7. Neuronal destruction and leucocytic infiltration occurred throughout the forebrain of SFV4-infected rats. A7-infected rats remained clinically normal although degenerate neurons and inflammatory changes were present primarily in the olfactory system. Following infection with either A7-SFV or SFV4, TUNEL-positive nuclei were seen in areas of leucocytic infiltration and among the poorly differentiated cells of the rostral migratory stream. Migrating cells had condensed nuclear chromatin, compacted cytoplasm and intact cellular membranes, characteristic of apoptosis, and were sparsely immunolabelled for viral antigen. In SFV4-infected rats, large numbers of contiguous neurones in forebrain areas exhibited cytoplasmic eosinophilia and karyolysis and were surrounded by phagocytic cells. Such neurones contained dense intracytoplasmic deposits of viral antigen and showed weak cytoplasmic TUNEL staining; electron microscopy showed membrane disruption, organelle disintegration, irregular chromatin condensation and cytoplasmic aggregation of virus particles. Bcl-2 staining was similar in infected and control rats and was most intense in randomly distributed Purkinje cells in the cerebellum; neurons in the olfactory bulbs were unstained. These findings indicate that during SFV encephalitis, infiltrating leucocytes and neural precursor cells undergo apoptosis whilst productively infected neurons undergo necrosis.
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PMID:Cell death mechanisms in the olfactory bulb of rats infected intranasally with Semliki forest virus. 1041 65

Circulating filarial proteins elicit strong immunologic reactions in humans leading to the chronic manifestations in human lymphatic filariasis such as lymphatic occlusion, fibrosis, edema, and in some cases, tropical pulmonary eosinophilia. Our earlier studies, in vitro, conclusively prove that filarial parasitic sheath proteins induce apoptosis in HEp2 cells, an epithelial cell line, by a pathway inhibitable by bcl2. The present findings provide evidence that c-myc activation triggers apoptosis in HEp2 cells and that it is also responsible for the burst of abortive proliferation at 6 d of treatment of HEp2 bcl2 cells that overexpress bcl2, with filarial parasitic sheath protein, demonstrating the interplay between the two genes c-myc and bcl2, wherein bcl2 acts by restoring the prosurvival signal to c-myc and keeping its apoptotic tendency in check. This study also indicates that bcl2 upregulates c-H-ras, engaging ras to bring about the suppression of apoptosis through protein tyrosine kinase elevation, thus promoting the survival of the HEp2 bcl2 cells. In addition to the activation of these "signal switches," we also observe that these cells release cytokines like IL-6 and IL-8 through the upregulation of c-fos, when exposed to filarial parasitic sheath protein, reflecting on the immunomodulatory capacity of the epithelium to elicit a host immune response by setting up a chemotactic gradient, attracting inflammatory cells to the site of infection.
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PMID:Epithelial cells release proinflammatory cytokines and undergo c-Myc-induced apoptosis on exposure to filarial parasitic sheath protein-Bcl2 mediates rescue by activating c-H-Ras. 1114 53

Allergic sensitisation of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa in humans is the adenoid and tonsils. Research done in respect to Waldeyer's ring on people dealing at the same time with allergy, is seldom the subject of dissertation in polish as well as world wide medical literature. In the enclosed dissertation, writers present the results of histopathological and immunohistochemical analysis of hyperplastic tonsils and adenoid, taken from children with coexisting atopy. The authors describe an immunohistochemical analyses of the hyperplastic human palatine tonsil. They present the expression of antigen CD3, CD20, CD45, CD68, EMA, SMA, Vimentin, Desmin, S-100, von Willebrand Factor, p35, Bcl-2, melanin, cytokeratin, estrogen receptor, progesteron receptor, kolagen IV and NSE in every region of pallatine tonsil. It is worthwhile to remark, that many of these cases, the presence of eosinophilia and subepithelial oedema was observed. Our immunohistochemical findings support the hypothesis that allergic sensitization takes place in the adenoid and tonsils. Furthermore, this study confirms that dendritic cells ad macrophages are involved and important in allergic disease.
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PMID:[Histopathological and immunological analysis of hyperplastic palatine tonsils and adenoids in children with coexisting atopic dermatitis]. 1459 70

The prognosis of Hodgkin's lymphoma has been improved over last 10 yr due to identification of prognostic parameters. These factors may predict the clinical outcome and therefore may have influence on the selection of appropriate treatment. In a cohort of 40 patients with Hodgkin's lymphoma of nodular sclerosis subtype, treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen, we analyzed prognostic relevance of the expression of Ki-67 and Bcl-2 at diagnosis as well as other clinical parameters: International Prognostic Score, bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate. Significance was tested according to response rate and overall survival. Patients with a high proliferative fraction (Ki-67 > 50%) had worse overall survival compared with those with low proliferation, 56% vs 91%. There was a correlation between Ki-67 positivity and the achievement of complete remission. Cox's multivariate model revealed that Ki-67 positivity at threshold of 50% was a significant independent prognostic factor. The Bcl-2 expression in less than 50% of tumor cells was detected in 65.5% of patients, and in a majority of cases it was associated with complete remission. Patients with high IPS had more progressive disease and shorter survival. Bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate had no significant influence on complete remission and survival. However, there was a marked divergence in survival curves after 4 yr follow-up for each of these parameters. Patients with high Ki-67, IPS > 3, bulky disease, tissue eosinophilia, and high sedimentation rate are at a higher risk of treatment failure and relapse and therefore might be eligible for other aggressive therapeutic approach.
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PMID:The expression of Ki-67 and Bcl-2 in Hodgkin's lymphoma: correlation with the International Prognostic Score and bulky disease: a study by the Serbian Lymphoma Study Group (SLG). 1767 11

The accumulation of eosinophils is a common feature of allergic airway inflammation and correlates with disease severity. In an ovalbumin (OVA)-induced murine model of allergic lung disease, CBA/Ca mice develop much lower levels of lung eosinophilia, lung oedema, mucus hypersecretion and airways obstruction than BALB/c and C57BL/6 strains. In this study these strains have been examined to identify mechanisms that control the recruitment and survival of eosinophils in the allergic lung. Following immunization with OVA, CBA/Ca mice developed a robust systemic allergic response, with high levels of total and OVA-specific IgE and increases in peripheral blood eosinophils. Lung eotaxin-1 levels and expression of CD18 on eosinophils recovered by bronchoalveolar lavage (BAL) were least pronounced in CBA/Ca mice, whereas mRNA for L-selectin was highest in eosinophils from C57BL/6 mice. Apoptosis of BAL eosinophils ex vivo was most pronounced in the CBA/Ca strain. BALB/c mice expressed the highest levels of the eosinophil growth and survival factor interleukin (IL)-5 in the lungs and BAL eosinophils from these animals expressed more of the anti-apoptotic proteins Bcl-xL and Bcl-2 than cells from the other strains. A combination of lower levels of recruitment and rapid apoptosis may therefore limit the accumulation of eosinophils and pathology in the lungs of CBA/Ca mice. In addition, although the level of pathology that developed in C57BL/6 and BALB/c mice was similar, some of the underlying mechanisms are likely to differ.
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PMID:Differential rates of apoptosis and recruitment limit eosinophil accumulation in the lungs of asthma-resistant CBA/Ca mice. 1858 44

Bid, a proapoptotic member of Bcl-2 family, is involved in Fas receptor signaling. Fas activation promotes human eosinophil cell death and is believed to accelerate the resolution of pulmonary Th2-driven allergic reaction in mice. We hypothesized that Bid would regulate eosinophil apoptosis and Ag-induced airway inflammation, particularly eosinophilia. C57BL/6 Bid(-/-) and wild-type mice were immunized and repeatedly challenged with OVA, and bronchoalveolar lavage (BAL) fluid, lung, and spleen were collected 4-240 h after the final challenge. Cultured BAL eosinophils from Bid-deficient mice showed resistance to Fas-mediated apoptotic DNA fragmentation, phosphatidylserine exposure, mitochondria depolarization, and caspase-3 activity. In addition, OVA-challenged Bid(-/-) mice had higher BAL eosinophilia and a lower proportion of BAL apoptotic eosinophils than Bid(+/+) mice. This was accompanied by augmented BAL levels of the eosinophilotactic cytokine, IL-5, and of the eosinophil-associated mediators, TGF-beta1 and fibronectin. Finally, cultured OVA-stimulated lung mononuclear cells and splenocytes from Bid-deficient mice showed increased release of the Th2-type cytokines, IL-4 and IL-5, but no change in cell number. We conclude that Bid modulates BAL eosinophilia by regulating both eosinophil apoptosis and Th2-type cytokine production.
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PMID:A role for Bid in eosinophil apoptosis and in allergic airway reaction. 1938 Aug 21