Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our studies were undertaken to evaluate early events associated with IFN expression and IFN-induced cellular changes in the spleen. Polyinosinic-polycytidylic acid (poly(I:C)) was used to induce IFN in C57BL/6 mice. Biologically active IFN was present in spleens and sera of poly(I:C)-treated mice as early as 3 h and peaked at 6 to 12 h posttreatment. Neutralization assays and Northern blot analyses demonstrated that IFN-beta was the form of IFN preferentially induced in the spleens. Immunohistochemical staining and in situ hybridization studies of splenic tissue sections demonstrated that, although many cells were induced to express low levels of IFN-beta, low frequency cells were particularly potent expressers of IFN-beta. Perivascular cells expressed high levels of IFN-beta. Other positive cells were localized in red pulp at early times and in white pulp at later times posttreatment. Histologic examination of splenic sections showed that the IFN production was accompanied by dramatic architectural changes. There were significant 1.4-fold increases in the proportion of white pulp area and > 50% decreases in red pulp leukocyte number. These architectural changes appeared at 6 h and lasted through 36 h after poly(I:C) treatment. They were not due to increased cell proliferation as splenic weights and cell yields were not elevated. The changes in splenic leukocyte distribution were shown to be a result of IFN induction as: 1) treatment with anti-IFN antibodies inhibited poly(I:C)-induced depletion of red pulp leukocytes, and 2) administration of purified IFN-beta induced both an increase in white pulp area and a decrease in red pulp leukocytes. Splenic leukocytes were labeled with the lipophilic fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate, to evaluate cell traffic after IFN induction. Poly(I:C) enhanced accumulation of cells in white pulp regions. In contrast to the 76 +/- 2 labeled cells that accumulated in 0.5 mm2 of white pulp area in control PBS-treated mice, 131 +/- 4 labeled cells accumulated in 0.5 mm2 of white pulp area in poly(I:C)-treated mice. The poly(I:C)-enhanced leukocyte accumulation in short term cell migration to white pulp regions was dependent on preexposure of both splenic leukocytes and recipient environments to the IFN inducer. These data demonstrate that poly(I:C) is a potent and rapid inducer of IFN-beta production by splenic cells and that IFN induces cellular redistribution in the spleen. The results suggest that margination of leukocytes into splenic white pulp may be another important immunoregulatory function of IFN.
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PMID:IFN induction and associated changes in splenic leukocyte distribution. 768 83

We determined whether an adenoviral vector-mediated murine IFN-beta gene therapy could eradicate established s.c. tumors produced by murine UV-2237m fibrosarcoma cells. The tumor cells were highly susceptible to infection by adenoviral vectors. Cells infected with 10 or 100 multiplicity of infection of AdCIFN-beta, an adenoviral vector encoding murine IFN-beta driven by the human cytomegalovirus promoter, expressed high levels of steady-state IFN-beta mRNA and produced 500 or 7,000 units of IFN-beta activity/10(6) cells/24 h, respectively. Infection of tumor cells with 30 multiplicity of infection of AdCIFN-beta (but not control AdCLacZ vector) inhibited in vitro tumor cell proliferation by 40-45%. Intralesional injection of 5 x 10(8) plaque-forming units of AdCIFN-beta (but not AdLacZ) eradicated established s.c. fibrosarcomas in syngeneic mice but not fibrosarcomas in nude mice. Mice cured of the disease developed systemic immunity against rechallenge with UV-2237m cells but not against another syngeneic tumor, the K-1735 M2 melanoma. Immunohistochemical analysis revealed that tumors injected with AdCIFN-beta contained more macrophages and CD4+ and CD8+ cells than did tumors injected with AdCLacZ or saline. Most cells in the PBS- and AdCLacZ-treated tumors stained positive for proliferating cell nuclear antigen, and few cells stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, AdCIFN-beta-treated tumors contained few proliferating cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling-positive cells. Taken together, our data demonstrate that IFN-beta gene therapy delivered by adenoviral vectors can be effective against fibrosarcomas.
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PMID:Eradication of primary murine fibrosarcomas and induction of systemic immunity by adenovirus-mediated interferon beta gene therapy. 1053 98

We determined whether the IFN-beta gene could suppress angiogenesis, tumor growth, and metastasis of human bladder transitional cell carcinoma. The highly tumorigenic and metastatic 253J B-V(R) human bladder transitional cell carcinoma (TCC) cell line (resistant to the antiproliferative effects of IFN-beta) was infected in vitro with adenoviral beta-galactosidase (Ad-LacZ), murine adenoviral IFN-beta (Ad-mIFN-beta), or human adenoviral IFN-beta (Ad-hIFN-beta) and implanted into the bladders of athymic nude mice. Ad-mIFN-beta and Ad-hIFN-beta were used because of the species specificity of IFN-beta. The transient production of mIFN-beta and hIFN-beta from the infected 253JB-V(R) tumor cells significantly inhibited tumorigenicity and spontaneous lymph node metastasis. Subsequently, the 253J B-V(R) cells were implanted into the subcutis of athymic nude mice, and established tumors were treated by direct intratumoral injection with Ad-mIFN-beta, Ad-hIFN-beta, Ad-LacZ, or PBS. By in situ hybridization (ISH) and immunohistochemical analysis (IHC), expression of hIFN-beta and mIFN-beta mRNA and protein within the tumors was demonstrated after Ad-hIFN-beta and Ad-mIFN-beta gene therapy, respectively. The therapy also induced necrosis in both the Ad-mIFN-beta- and Ad-hIFN-beta-treated tumors. IHC revealed decreased tumor cell proliferation and the sequestration of activated macrophages within the tumors after Ad-mIFN-beta therapy. In addition, the expression of the proangiogenic factors bFGF, and MMP-9 protein (by IHC) was significantly down-regulated by Ad-hIFN-beta gene therapy. Double-immunofluorescent IHC for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) and CD-31 demonstrated tumor and endothelial cell apoptosis in those tumors treated with Ad-hIFN-beta gene therapy. Tumor-induced angiogenesis, as determined by the microvessel density, was decreased in tumors treated with both Ad-mIFN-beta and Ad-hIFN-beta. These data suggest that the inhibition of tumorigenicity and the metastasis of the 253J B-V(R) cells after infection with Ad-IFN-beta is caused by the inhibition of angiogenesis and the activation of host effector cells.
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PMID:Inhibition of tumorigenicity and metastasis of human bladder cancer growing in athymic mice by interferon-beta gene therapy results partially from various antiangiogenic effects including endothelial cell apoptosis. 1194 41

We have previously reported that heat-killed Lactobacillus plantarum L-137 (HK-LP) stimulates macrophage/dendritic cells to produce T helper (Th) 1-related cytokines in vitro and in vivo in mice. We here examined the effect of oral administration of HK-LP on protection against influenza virus infection in mice. C57BL/6 mice were orally given HK-LP from day -7 to 7 and intranasally infected with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) at 100 pfu on day 0. The survival time was significantly prolonged in mice treated with HK-LP than that in mice treated with PBS as controls. The viral titers in the lung were significantly lower in mice treated with HK-LP than controls at the early stage after influenza virus infection. An appreciable level of interferon (IFN)-beta was detected in the serum of mice treated with HK-LP, while no IFN-beta was detected in controls after influenza infection. Our results suggest that HK-LP, a potent IFN-beta inducer, is useful for prevention against influenza infection.
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PMID:Oral administration of heat-killed Lactobacillus plantarum L-137 enhances protection against influenza virus infection by stimulation of type I interferon production in mice. 1941 Jun 59