Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiratory syncytial virus (RSV) infection is an important cause of lower respiratory tract illness, the severity of which may be partly due to cellular recruitment. RSV infection activates chemokine secretion from airway epithelial cells by largely unknown mechanisms. We investigated the regulation of RSV-induced activation of the chemokine RANTES in the bronchial epithelial cell line BEAS-2B and primary normal human tracheobronchial epithelial cultures. RANTES protein and mRNA were detected at 24 h and up until 72 h from cultures of BEAS-2B infected with replicating virus, but not with UV-inactivated RSV. RSV infection of BEAS-2B or normal human tracheobronchial epithelial cells stimulated NF-kappa B translocation to the nucleus and binding to the RANTES-specific kappa B-binding sequences within 2 h, with levels peaking at 24 h. Supershift assays indicated that binding was due to p50/p65 heterodimers. BEAS-2B cells were transfected with a replication-deficient adenoviral vector, expressing a mutated, nondegradable form of I kappa B alpha. I kappa B alpha overexpression specifically blocked NF-kappa B translocation and inhibited mRNA accumulation and secretion of RANTES induced by RSV or TNF-alpha plus IFN-gamma. Adenoviral transfection did not interfere with RSV replication or significantly induce apoptosis. Further, a control adenovirus, expressing the beta-galactosidase gene, did not alter cellular functions. Thus, NF-kappa B nuclear translocation is a critical step in RSV induction of RANTES secretion. Elucidating the mechanisms of cellular activation by RSV and targeting specific areas may lead to novel therapeutic approaches in the treatment of RSV.
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PMID:Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha. 967 Sep 82

Herpes simplex virus amplicon vectors expressing RANTES (HSVrantes) and the T-cell costimulatory ligand B7.1 (HSVB7.1) were studied for their ability to elicit a tumor-specific T-cell response in a murine lymphoma model. HSVB7.1- and HSVrantes-transduced EL4 cells expressed high levels of B7.1 and RANTES as analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. Inoculation of ex vivo HSVB7.1 transduced cells in syngeneic mice resulted in regression of both transduced cells and nontransduced cells inoculated contralaterally. Direct intratumoral injection of HSVB7.1 and/or HSVrantes alone or in combination into established EL4 tumors led to complete tumor regression in injected tumors as well as in nontransduced contralaterally implanted tumor, whereas control tumors or tumors injected with HSVlac expressing beta-galactosidase did not regress. Maximal protection was achieved with combined injection of HSVB7.1 and HSVrantes; mice showing tumor regression were resistant to rechallenge with parental EL4 cells, and tumor cell-specific cytolytic T-cell activity was observed in mice demonstrating regression. HSV amplicon-mediated delivery of immune effector molecules may represent a useful strategy for immunotherapy in the setting of pre-existing tumor.
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PMID:Eradication of pre-established lymphoma using herpes simplex virus amplicon vectors. 988 27

To determine whether C-C chemokines play an important role in the phenotype switch of human immunodeficiency virus (HIV) from CCR5 to CXCR4 usage during the course of an infection in vivo, macrophage inflammatory protein (MIP)-1alpha-resistant variants were isolated from CCR5-tropic (R5) HIV-1 in vitro. The selected variants displayed reduced sensitivities to MIP-1alpha (fourfold) through CCR5-expressing CD4-HeLa/long terminal repeat-beta-galactosidase (MAGI/CCR5) cells. The variants were also resistant to other natural ligands for CCR5, namely, MIP-1beta (>4-fold) and RANTES (regulated upon activation, normal T-cell expressed and secreted) (6-fold). The env sequence analyses revealed that the variants had amino acid substitutions in V2 (valine 166 to methionine) and V3 (serine 303 to glycine), although the same V3 substitution appeared in virus passaged without MIP-1alpha. A single-round replication assay using a luciferase reporter HIV-1 strain pseudotyped with mutant envelopes confirmed that mutations in both V2 and V3 were necessary to confer the reduced sensitivity to MIP-1alpha, MIP-1beta, and RANTES. However, the double mutant did not switch its chemokine receptor usage from CCR5 to CXCR4, indicating the altered recognition of CCR5 by this mutant. These results indicated that V2 combined with the V3 region of the CCR5-tropic HIV-1 envelope modulates the sensitivity of HIV-1 to C-C chemokines without altering the ability to use chemokine receptors.
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PMID:Involvement of both the V2 and V3 regions of the CCR5-tropic human immunodeficiency virus type 1 envelope in reduced sensitivity to macrophage inflammatory protein 1alpha. 1064 51

Adenoviral gene transfer is a potential ex vivo gene therapy for islet transplantation. However, the immunogenicity of adenoviral vectors can potentially impair vector efficacy in transplants where long-term gene expression is required. We investigated the effect of this antiviral immunity on vector expression and islet graft function. Syngeneic murine islets transduced with adenovirus encoding beta-galactosidase (AdCMVnt-betagal) were transplanted under the renal capsule. At different time points after transplant, blood glucose and glucose tolerance, intragraft cellular infiltration and IgG, IgM productions, and expression of transgene, cytokines and chemokines/receptors were assessed. Splenocytes and sera were analyzed to evaluate the systemic anti-adenoviral immune response. Diabetes was reversed in 1 day in recipients of a marginal amount (200) of untransduced islets, while AdCMVnt-betagal-transduced islets failed to reverse diabetes until 10 days post-transplant (p</=0.048). A profound and progressive infiltration with CD4(+), CD8(+) cells, natural killer cells, and macrophages was identified in adenovirus transduced grafts, which paralleled a decline in beta-gal expression. However, this did not extinguish transgene and insulin expression, which persisted for over 3 months. Glucose tolerance was impaired in transduced grafts at 25 days compared with non-transduced grafts (p=0.008), but was equivalent at 3 months (p=0.275) post-transplant. Intragraft interferon (IFN)-gamma and RANTES mRNA expression was not different between transduced and untransduced islet grafts, despite an increased expression of CC chemokine receptor 5 (CCR5). No significant splenocyte IFN-gamma and interleukin (IL)-4 production or serum anti-adenoviral antibodies were discovered albeit IgM antibody was detected in transduced grafts. Transduction of islets with adenoviral vectors results in overt local inflammation of islet grafts and inhibits early graft function. However, long-term graft function is preserved, and transgene expression persists. Thus, antivector immunity leads to neither loss of islet graft nor eradication of vector.
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PMID:Immunity to islet grafts transduced with adenovirus vectors does not inhibit long-term islet function. 1922 10