Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.
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PMID:Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro. 213 61

The purpose of this investigation was to determine whether mouse lung fibroblast subsets have the ability to produce nitric oxide (NO), and if so, to characterize the induction and effects of its synthesis. Previously, we isolated Thy1+ and Thy1- subpopulations of mouse lung fibroblasts, which differ in terms of cytokine production, morphology, response to cytokines and radiation, and ability to present antigen to T lymphocytes. When treated with the proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-1 alpha, these fibroblast lines produce micromolar quantities of NO2- and NO3-, two stable end products of the NO pathway. A combination of all three cytokines provided the greatest induction, and there was no measurable production of NO in unstimulated cells. Thy1+ fibroblasts have fewer requirements for induction of NO production than the Thy1- line, in that NO production could be induced by only two of the above cytokines, where the Thy1- fibroblasts required all three. Inducible NO synthase (iNOS) mRNA was shown to be present by the reverse transcriptase-polymerase chain reaction as early as 2 hr after cytokine treatment in both cell lines. Addition of the NO synthase inhibitors NG-monomethyl-L-arginine and aminoguanidine inhibited production of NO2- and NO3-, but not iNOS mRNA. This inhibition was partially reversed by the addition of an excess of L-arginine. Interestingly, inhibition of NO synthesis was shown to decrease IL-6 production by more than 50% in cytokine-treated Thy1+ fibroblasts. These results indicate for the first time that Thy1+ and Thy1- mouse lung fibroblast subsets have the capability to produce NO to differing extents in response to cytokines and may therefore play an important role in the inflammatory response in the lung as well as in the progression of lung disease.
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PMID:Induction of nitric oxide synthase in subsets of murine pulmonary fibroblasts: effect on fibroblast interleukin-6 production. 751 14

Interleukin (IL)-7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma-bearing mice. Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL-7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 +/- 0.2 degrees C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, granulocyte colony stimulating factor (G-CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL-7 in combination with LH. Survival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL-7 plus LH. Increases in levels of IL-1 alpha, IL-6, tumor necrosis factor (TNF alpha) and interferon (IFN gamma) were associated with an increase in the survival of tumor-bearing mice treated with IL-7 and/or LH. These results suggest that changes in T-cell, NK cell and cytokines such as IL-1 alpha, IL-6, TNF-alpha and IFN-gamma in response to IL7 and/or LH might account for prolonged survival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.
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PMID:Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells. 824 52

Rat thymic dendritic cells (TDC) were isolated from thymic cell suspension by Nycodenz gradients of different densities and osmolarities. After cultivation of these cells for 3 days in the conditioned medium (TE-R 2.5 + HT supernatant) prepared by cocultivation of a medullary thymic epithelial cell line (TE-R 2.5) and hydrocortisone resistant thymocytes, the purity (75-85%) and survival of TDC significantly increased. The supernatant contained moderate activities of IL-1 and IL-6, low levels of TNF-alpha and IL-2 and factor(s) that strongly stimulated the proliferation of a mouse macrophage cell line RAW 264.7. TDC survival in culture was significantly increased by GM-CSF and decreased by IL-6 and IFN-gamma. The phenotype of TDC was studied by flow cytometry using a panel of monoclonal antibodies (mAb) to rat cell surface markers. It was found that almost all freshly isolated TDC expressed major histocompatibility complex (MHC) class I and class II molecules as well as CD45. Most TDC were LFA-1 (CD11a)+, CD18+, ICAM-1 (CD54)+ and CD53 (OX- 44)+, but only certain subsets expressed CD11b and thymocyte markers Thy1, CD2, CD4 and CD8. Upregulation in the expression of almost all the markers was observed after cultivation of TDC. In addition, cultivated, but not freshly isolated TDC expressed CD25 (IL-2R alpha) and CD45RC (OX-22) molecules. Cultivated TDC had strong accessory function in autologous thymocyte proliferation.
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PMID:Isolation, cultivation and phenotypic characterization of rat thymic dendritic cells. 862 79

The most potent virulence factor of Pseudomonas aeruginosa, its exotoxin A (PEA), inhibits protein synthesis, especially in the liver, and is a weak T cell mitogen. This study was performed to correlate hepatotoxic and possible immunostimulatory features of PEA in vivo. Injection of PEA to mice caused hepatocyte apoptosis, an increase in plasma transaminase activities, and the release of TNF, IFN-gamma, IL-2, and IL-6 into the circulation. Most strikingly, liver damage depended on T cells. Athymic nude mice or mice depleted of T cells by anti-Thy1.2 mAb pretreatment failed to develop acute hepatic failure, and survival was significantly prolonged following T cell depletion. Neutralization of TNF or lack of TNF receptors prevented liver injury. In the liver, TNF was produced by Kupffer cells before hepatocellular death occurred. After T cell depletion, Kupffer cells failed to produce TNF. Transaminase release was significantly reduced in perforin knockout mice, and it was even elevated in lpr/lpr mice. These results demonstrate that PEA induces liver damage not only by protein synthesis inhibition but also by TNF- and perforin-dependent, Fas-independent, apoptotic signals.
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PMID:Acute hepatotoxicity of Pseudomonas aeruginosa exotoxin A in mice depends on T cells and TNF. 982 May 56

Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow (BM) failure. We have previously shown that stem cells from the FA group C mouse model have lower long-term primary and secondary reconstitution ability, and that bone marrow of Fancc(-/-) mice contained fewer lineage-negative (Lin(-))Thy1.2(low)Sca-1(+)c-kit(+) CD34(+) cells but normal levels of Lin(-)Thy1.2(low)Sca-1(+)c-kit(+)CD34(-) primitive cells. These data suggest that CD34(+) primitive cells have either a lower growth or differentiation potential, or that these cells have greater apoptosis levels. To investigate the role Fancc might have on the growth and differentiation potentials of primitive hematopoietic stem cells, we used a single-cell culture system and monitored cell viability, doubling potential, and apoptosis levels of Fancc(-/-) primitive Lin(-)Thy1.2(-)Sca-1(+) (LTS)-CD34(+) and LTS-CD34(-) stem cells. Results showed that Fancc(-/-) LTS-CD34(-) and LTS-CD34(+) cells had altered growth and apoptosis responses to combinations of stimulatory cytokines, most dramatically in response to a combination of factors that included interleukin-3 (IL-3) and IL-6. In addition, Fancc(-/-) LTS-CD34(-) and LTS-CD34(+) cells showed a lower differentiation potential than Fancc(+/+) cells. These results support a role for Fancc in the growth and differentiation of primitive hematopoietic cells and suggest that an altered response to stimulatory cytokines may contribute to BM aplasia in FA patients.
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PMID:Hematopoietic stem cells from fancc(-/-) mice have lower growth and differentiation potential in response to growth factors. 1235 14

To observe whether bone marrow stromal cell line QXMSC1 (H-2(d)) engineered to secrete IL-3 and IL-6 can improved the hematopoiesis in allogeneic bone marrow transplantation (allo-BMT) mice, the stromal cell line QXMSC1IL-3/IL-6 was established by QXMSC1 cells transduced with the recombined retrovirus vector pL3SN containing mouse IL-3 cDNA and pL6SN containing human IL-6 cDNA. The lethally irradiated C57BL/6 (H-2(b)) mice were engrafted with bone marrow cells (1 x 10(7) cells/mouse BALB/c mice, H-2(d)) in which T cells were depleted by anti-Thy1.2 monoclonal antibody adding complement, and QXMSC1IL-3/IL-6 cells (5 x 10(5)/mouse) were co-infused at same time. The hematopoiesis of recipient mice was observed in 20 and 40 days post-transplantation. Blood RBC and WBC were counted, and nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM were assayed in recipient bone marrow. Results showed that IL-3 and IL-6 were stably expressed in QXMSCQIL-3/IL-6 cells. Compared with BMT and co-infusion with QXMSC1 or QXMSC1 pLXSN cell groups, co-graft with QXMSC1IL-3/IL-6 cells increased the number of blood RBC and WBC in the recipients, and also significantly increased nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM in recipient bone marrow. It is concluded that the marrow stromal cells transduced with IL-3/IL-6 cDNA improve the hematopoiesis in allo-BMT mice. Co-graft with QXMSC1IL-3/IL-6 cells has synergistic effect in accelerating hematopoietic reconstitution.
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PMID:[Accelerating hematopoietic recovery in allogeneic bone marrow transplantation mice by co-infusion of marrow stromal cells transduced with dual genes of IL-3/IL-6]. 1251 31

Studies have shown that lipoxin A(4) (LXA(4)) inhibited proliferation of mesangial cells in vitro induced by platelet-derived growth factor, epidermal growth factor, leukotriene D(4) or tumor necrosis factor-alpha. In this study, we investigated the protective effects of 15(R/S)-methyl-LXA(4) on mesangioproliferative nephritis in rats and the signal transduction involved in actions of 15(R/S)-methyl-LXA(4). Mesangioproliferative nephritis was induced by a single intravenous injection of the mouse monoclonal anti-Thy1.1 antibodies. The nephritic rats were treated by intravenous injection of 15(R/S)-methyl-LXA(4) every 8h until the rats were sacrificed. There were increments in glomerular infiltration of leukocytes, expressions of protein and mRNA of interleukin (IL)-1beta and IL-6, activities of nuclear factor-kappaB (NF-kappaB) in nephritic rats from day 1 to 4 after induction of nephritis. The enhanced proteinuria, proliferation score of mesangial cells, glomerular proliferating cell nuclear antigen (PCNA) positive cells, activities of phosphorylated phosphoinositide 3-kinase (PI3-K), Akt(1), alpha-smooth muscle actin (alpha-SMA) and signal transducer and activator of transcription 3(STAT(3)), and reduced expression of p27(kip1) were found on day 4 after induction of nephritis. Treatment of nephritic rats with 15(R/S)-methyl-LXA(4) significantly reduced the protenuria, glomerular infiltration of leukocyte, expressions of protein and mRNA of IL-1beta and IL-6, proliferation score of mesangial cells, glomerular PCNA positive cells, activities of phosphorylated PI3-K, Akt(1), alpha-SMA, NF-kappaB and STAT(3), and ameliorated the decrement in p27(kip1) induced by anti-Thy1.1 antibodies. Protective effects of 15(R/S)-methyl-LXA(4) on nephritis induced by anti-Thy1.1 antibodies were related to PI3-K/Akt(1)/p27(kip1)/cyclin pathway, STAT(3) and NF-kappaB pathway-dependent signal transduction.
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PMID:Signal transduction involved in protective effects of 15(R/S)-methyl- lipoxin A(4) on mesangioproliferative nephritis in rats. 1732 90

This study was aimed to investigate the biological characteristics of osteoblasts and their hematopoietic supportive function by using human fetal osteoblastic cell line 1.19 (hFOBs) as a model. The pluripotency markers (Oct-4, Rex-1, hTERT) of hFOBs were analyzed by RT-PCR, the multilineage differentiation experiments were conducted in vitro. Flow cytometry (FCM) was used to identify the surface markers of hFOBs, and RT-PCR was used to analyze their hematopoietic cytokine expression in comparison with bone marrow mesenchymal stem cell (BM-MSC). The results showed that hFOBs expressed several ESC pluripotency markers including Oct-4 and Rex-1, except hTERT. Moreover, hFOBs could also undergo multilineage differentiation into the mesodermal lineages of adipocytic cell types in addition to its predetermined pathway, the mature osteoblast. Both hFOBs and BM-MSC expressed CD44, CD73 (SH3), CD105 (SH2) and CD90 (Thy1), and lack expression of CD34, CD45, or HLA-DR surface molecules. In addition, both hFOBs and BM-MSC expressed SCF, IL-6, and SDF-1alpha mRNA, but only hFOBs could express GM-CSF and G-CSF. It is concluded that human fetal osteoblastic cell line 1.19 may provide a good model to study the osteoblastic regulation role in hematopoiesis in vitro.
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PMID:[Biological characteristics of human fetal osteoblastic 1.19 cell line]. 1842 61

We demonstrate immunomodulatory effects, especially those involving murine intestinal IgA secretion, in Peyer's patch cells following oral administration of Bifidobacterium immunomodulator (BIM) derived from sonicated B. pseudocatenulatum 7041. BALB/c mice were administered BIM orally for 7 consecutive days. The PP cells demonstrated upregulated secretion of total IgA including BIM-specific IgA following BIM administration. In observing the response of PP cells co-cultured with BIM, we found enhanced secretion of interferon-gamma (IFN-gamma) and interleukin (IL)-6 in the CD4(+) T cells. In contrast, IL-12 secretion by Thy1.2(-) PP cells was enhanced, but secretion of IFN-gamma, IL-5, and IL-6 was not significantly affected. Furthermore, the population of CD4(+) CD45RB(high) T cells in PP increased following oral administration of BIM. These data suggest that CD4(+) T cells were affected by BIM administration. Overall, the results show that oral administration of BIM induced CD4(+) PP cells to change their expression of cell surface antigen and cytokine production.
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PMID:Characteristic Immune Response in Peyer's Patch Cells Induced by Oral Administration of Bifidobacterium Components. 1900 46


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