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

Three major inhibitors of the NF-kappaB/Rel family of transcription factors, IkappaBalpha, IkappaBbeta, and IkappaBepsilon, have been described. To examine the in vivo role of the most recently discovered member of the IkappaB family, IkappaBepsilon, we generated a null allele of the murine IkappaBepsilon gene by replacement of all coding sequences with nlslacZ. Unlike IkappaBalpha nullizygous mice, mice lacking IkappaBepsilon are viable, fertile, and indistinguishable from wild-type animals in appearance and histology. Analysis of beta-galactosidase expression pattern revealed that IkappaBepsilon is mainly expressed in T cells in the thymus, spleen, and lymph nodes. Flow cytometric analysis of immune cell populations from the bone marrow, thymus, spleen, and lymph nodes did not show any specific differences between the wild-type and the mutant mice, with the exception of a reproducible 50% reduction of the CD44-CD25+ T cell subspecies. The IkappaBepsilon-null mice present constitutive up-regulation of IgM and IgG1 Ig isotypes together with a further increased synthesis of these two isotypes after immunization against T cell-dependent or independent Ags. The failure of observable augmentation of constitutive nuclear NF-kappaB/Rel-binding activity is probably due to compensatory mechanisms involving IkappaBalpha and IkappaBbeta, which are up-regulated in several organs. RNase-mapping analysis indicated that IL-1alpha, IL-1beta, IL-1Ra, and IL-6 mRNA levels are constitutively elevated in thioglycolate-elicited IkappaBepsilon-null macrophages in contrast to GM-CSF, G-CSF, and IFN-gamma, which remain undetectable.
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PMID:IkappaBepsilon-deficient mice: reduction of one T cell precursor subspecies and enhanced Ig isotype switching and cytokine synthesis. 1057 Feb 87

The experiments in this paper were designed to examine the therapeutic effects of adenoviral-mediated gene transfer of IFN-gamma into a mouse model of an established metastatic brain tumor. Temperature-sensitive replication-defective adenovirus was generated for gene transfer of IFN-gamma (AdIFN) and beta-galactosidase (AdBGAL) cDNAs in vivo. In this model, treatment with AdIFN elicits prolonged survival times and brain tumor rejection. Evidence against an immune-mediated response accounting for this result include: 1) absence of a memory immune response upon challenge, 2) lack of antitumor effects at sites distal to inoculation of AdIFN, and 3) preservation of the therapeutic effects of AdIFN in scid and beige mice and in inducible NO synthase (iNOS) knockouts. High concentrations of IFN-gamma do not inhibit tumor growth in vitro making it unlikely that the antitumor effect of this treatment acts directly on the growth of the tumor cells. However, gene transfer of IFN-gamma inhibits neovascularization of the tumor in a 3LL-Matrigel assay in vivo, and AdIFN induces apoptosis of endothelial cells in vivo, supporting the idea that AdIFN represses tumor growth by inhibiting angiogenesis. The substantial non-immune-mediated therapeutic benefits of AdIFN in animals paves the way for devising novel strategies for treating human brain tumors.
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PMID:Gene transfer of IFN-gamma into established brain tumors represses growth by antiangiogenesis. 1060 14

To determine whether an ongoing response to Leishmania major would affect the response to a non-cross-reacting, non-leishmanial antigen, susceptible BALB/c mice and resistant C3H mice were infected with L. major parasites expressing Escherichia coli beta-galactosidase (beta-GAL); this parasite was designated L. major-betaGAL. BALB/c and C3H mice responded to infection with L. major-betaGAL by mounting a CD4 T-cell response to both parasite antigens and to the reporter antigen, beta-GAL. The phenotypes of these T cells were characterized after generating T-cell lines from infected mice. As expected, BALB/c mice responded to infection with L. major-betaGAL by producing interleukin 4 in response to the parasite and C3H mice produced gamma interferon (IFN-gamma) in response to the parasite and beta-GAL. Interestingly, however, BALB/c mice produced IFN-gamma in response to beta-GAL. Taken together, these results demonstrate that priming of IFN-gamma-producing cells can occur in BALB/c mice despite the fact the animals are simultaneously mounting a potent Th2 response to L. major.
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PMID:Priming of a beta-galactosidase (beta-GAL)-specific type 1 response in BALB/c mice infected with beta-GAL-transfected Leishmania major. 1063 50

We evaluated the effectiveness of the Helios gene gun system, a recently developed, commercially available gene gun device. Following skin transfection with beta-galactosidase or interleukin-12 cDNA using the gene gun, beta-galactosidase expression was detected exclusively in the epidermal cell layer, and transgene expression of IL-12 cDNA was maximal 2 days post-transfection and remained detectable for at least 5 additional days. Furthermore, particle-mediated delivery of IL-12 cDNA into epidermal cells overlying an intradermal tumor resulted in a significant suppression of tumor growth of Lewis lung carcinoma. Appreciable levels of IFN-gamma production were readily detected at the skin transfection site, and were induced from splenocytes and lymph node cells in the IL-12 treated mice. These results show that in vivo delivery of IL-12 cDNA into skin by the Helios gene gun device can have a useful routine application for cancer therapy research.
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PMID:Particle-mediated gene transfer of murine interleukin-12 cDNA suppresses the growth of Lewis lung carcinoma. 1065 92

We evaluated whether immune responses stimulated by Salmonella vaccine carriers can be modulated by using different promoters to drive antigen expression. Mice were orally immunized with strains transfected with plasmids carrying beta-galactosidase (beta-gal) under the control of either a constitutive or an in vivo-activated promoter. While alpha-gal-reactive IgG1, IgG2a, IgG2b and IgG3 were detected in sera of mice immunized with Salmonella expressing constitutively beta-gal, higher titers dominated by IgG2a and IgG2b were detected in sera when the in vivo-activated promoter was used. beta-gal-specific proliferative responses of spleen-derived CD4+ T lymphocytes were similar in both groups. However, CD4+ T lymphocytes from mice immunized with the constitutive promoter secreted IL-4, IL-5, IL-6, IL-10 and IFN-gamma (Th1/Th2 pattern), whereas CD4+ cells mainly secreted IFN-gamma (Th1 pattern) when the second construct was used. The spleens of all immunized mice contained beta-gal-reactive CD8+ CTL precursors. The vaccine prototypes were tested for their capacity to control seeding and/or development within the lung of an intravenously delivered aggressive fibrosarcoma transfected with beta-gal. Reduced metastasis and significantly increased mean survival times were observed in all vaccinated mice. However, protection was improved when the carrier expressed beta-gal upon infection (80 % versus 50% survival, p < 0.05).
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PMID:Modulation of host immune responses stimulated by Salmonella vaccine carrier strains by using different promoters to drive the expression of the recombinant antigen. 1074 91

Interleukin-10 (IL-10) and interleukin-4 (IL-4), two Th2-derived cytokines, are molecules with anti-inflammatory and immunodeviating properties whose direct expression in allografts may prolong graft survival. Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of beta-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 10(9) p.f.u. of AdIL-10 (16.6 +/- 3.2 days, P < 0.05), but not AdIL-4 (9.8 +/- 1.6 days), compared with Addl324-treated (9.3 +/- 3.3 days) or untreated groups (7.8 +/- 1.5 days). Immunohistochemical analysis of allografts after gene transfer of IL-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of CD8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-gamma production but significantly increased transforming-growth factor beta 1 (TGF-beta 1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival.
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PMID:Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats. 1075 24

Nuclear retinoid receptors - retinoic acid inducible transcription factors - participate in pathways influencing many components of the immune system. In the present study in vivo effects of DNA-based immunization of mice on binding parameters of all-trans retinoic acid receptors (RARs) in spleen cell nuclei was investigated. A eucaryotic expression vector encoding the gene for the model enzyme beta-galactosidase of Escherichia coli (pCMV-beta) was used for intradermal injection. Furthermore, immunostimulatory CpG motifs, which stimulate the expression of various cytokines and may serve as a 'danger signal' for the mammalian immune system, were coinjected as oligodeoxynucleotides. The results demonstrate that the concentration of RARs was significantly reduced in the late phase of the primary immune response (21 days after injection of plasmid DNA-indicated by high affinity IgG antibodies and IFN-gamma expression). Coinjection of CpG motifs did not change the course of the humoral response but enhanced and accelerated the proliferative response and expression of IFN-gamma, which correlated with the reduced RARs concentration.
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PMID:DNA immunization in vivo down-regulates nuclear all-trans retinoic acid receptors in mouse spleen cells. 1094 Apr 89

Immunostimulatory DNA sequences (ISS) are a potent Th1 adjuvant. We hypothesized that conjugation of ISS to protein antigens would strongly enhance their immunogenicity because both antigen and adjuvant (ISS) would be delivered to the same locale/antigen-presenting cell. To test this hypothesis, we conjugated a 22-mer immunostimulatory oligodeoxynucleotide (ISS-ODN) to two test antigens of differing intrinsic immunogenicity, namely Escherichia coli beta-galactosidase and the HIV-1 envelope glycoprotein gp120. We show that the antigen-ISS conjugates rapidly induce Th1 cells secreting high levels of IFN-gamma, strong CTL activity, and high titer IgG2a and HIV-neutralizing antibodies, exceeding gene and protein vaccination alone or immunization with mixtures of antigen and ISS-ODN. The data suggest that this procedure generates a novel and unique vaccine that rapidly triggers strong humoral and cell-mediated immunity.
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PMID:Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. 1094 Aug 83

Previous work has implicated the cytokine leukemia inhibitory factor (LIF) in cutaneous inflammation, although results have differed as to whether LIF is pro- or anti-inflammatory in this setting. We examined edema, inflammatory cell infiltration, and cytokine responses following CFA injection in the adult mouse footpad. Inflammatory cell infiltration and edema are significantly enhanced when CFA is injected in LIF knockout mice as compared with injection of wild-type littermates. Moreover, local injection of an adenoviral vector encoding LIF suppresses both measures of inflammation. In contrast, injection of an adenoviral vector encoding beta-galactosidase has no discernable effect on inflammation. In addition, comparison of the CFA responses in LIF knockout vs wild-type skin reveals that LIF is an important regulator of IL-1beta, IL-6, IL-7, IL-2Ralpha, and IFN-gamma in cutaneous inflammation. These and our previous data indicate that both endogenous and exogenous LIF are anti-inflammatory in the CFA model and that LIF is a key regulator of the cytokine cascade. The results also indicate that adenoviral gene delivery can be an effective therapeutic approach in this paradigm.
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PMID:Studies using leukemia inhibitory factor (LIF) knockout mice and a LIF adenoviral vector demonstrate a key anti-inflammatory role for this cytokine in cutaneous inflammation. 1116 Feb 55

Nephrotoxic nephritis (NTN) is characterized by acute macrophage-dependent inflammation and serves as a model of human glomerulonephritis. In this study we have transfected rat macrophages with recombinant adenovirus expressing IL-4 (Ad-IL4) and demonstrated that these transfected macrophages develop fixed properties as a result of transfection, as shown by reduced NO production in response to IFN-gamma and TNF. Ad-IL4-transfected macrophages localized with enhanced efficiency to inflamed glomeruli after renal artery injection in rats with NTN compared with adenovirus expressing beta-galactosidase (Ad-beta gal)-transfected macrophages and produced elevated levels of the cytokine in glomeruli in vivo for up to 4 days. The delivery of IL-4-expressing macrophages produced a marked reduction in the severity of albuminuria (day 2 albuminuria, 61 +/- 15 mg/24 h) compared with unmodified NTN (day 2 albuminuria, 286 +/- 40 mg/24 h; p < 0.01), and this was matched by a reduction in the number of ED1-positive macrophages infiltrating the glomeruli. Interestingly, the injection of IL-4-expressing macrophages into single kidney produced a marked reduction in the numbers of ED1-positive macrophages in the contralateral noninjected kidney, an effect that could not be mimicked by systemic delivery of IL-4-expressing macrophages. This implies that the presence of IL-4-expressing macrophages in a single kidney can alter the systemic development of the inflammatory response. Macrophage transfection and delivery provide a valuable system to study and modulate inflammatory disease and highlight the feasibility of macrophage-based gene therapy.
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PMID:Macrophages transfected with adenovirus to express IL-4 reduce inflammation in experimental glomerulonephritis. 1125 34


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