Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neospora caninum is an obligate intracellular protozoan parasite which is efficiently transmitted transplacentally in cattle where it may cause abortion. A pregnant mouse model was used to characterise the immune response following N. caninum infection; the response in non-pregnant and pregnant mice was compared. Spleen cells from both infected/non-pregnant and infected/pregnant mice produced interferon-gamma, interleukin-12 and tumour necrosis factor alpha; however, the levels of these Th1 cytokines were lower in infected/pregnant mice. Infected/non-pregnant and infected/pregnant mice also produced the Th2 cytokine interleukin-10; however, there was no trend toward a decrease of this in pregnant mice. Interleukin-4 was exclusively produced at high levels by infected/pregnant mice and thus appears responsible for the observed decline in Th1 cytokine production in pregnant mice. A bias towards Th2 cytokines such as IL-4 and IL-10 is normally associated with the maintenance of a viable pregnancy, and not with the control of protozoal infections. Consequently, the importance and role of cytokines and cell-mediated immunity in the control of transplacental transmission and foetal loss due to N. caninum infection are discussed.
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PMID:The cell-mediated immune response to Neospora caninum during pregnancy in the mouse is associated with a bias towards production of interleukin-4. 1511 Oct 94

Spleen transplantation is the treatment of choice for some diseases, such as hemophilia A. However, the risk and intensity of rejection after spleen transplantation is greater and more difficult to control than other types of transplant. In the present study, we demonstrated that perfusion of IL-4 expression plasmids into donor spleens pretransplantation led to overexpression of IL-4 and downregulation of IFN-gamma in situ, associated with delayed acute rejection of the allograft. Gene transfer of IL-4 may represent a potential therapeutic approach to induce tolerance to splenic allografts.
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PMID:Gene transfer of interleukin-4 delays acute rejection of splenic allografts in rats. 1525 93

Diabetes mellitus is an important predisposing factor for tuberculosis. The aim of this study was to investigate the mechanism underlying this association using a murine model. Mice with streptozotocin-induced diabetes mellitus were prone to Mycobacterium tuberculosis infection, as indicated by increased numbers of live bacteria in lung, liver and spleen. In diabetic mice, the levels of IL-12 and IFN-gamma in the lung, liver and spleen were lower than those in control animals on day 14 postinfection, while the opposite was true for IL-4 levels in the lung and liver. The expression pattern of inducible nitric oxide synthase (iNOS), in the two mice types was as for IL-12 and IFN-gamma. In addition, peritoneal exudate cells obtained from diabetic mice produced lower amounts of IL-12 and NO than those from control mice, when stimulated in vitro with M. bovis BCG. Spleen cells from diabetic mice infected with M. tuberculosis produced a significantly lower amount of IFN-gamma upon restimulation with purified protein derivatives (PPD) than those from infected nondiabetic mice. Interestingly, addition of high glucose levels (33 mM) to the cultures of PPD-restimulated spleen cells reduced the synthesis of IFN-gamma only in diabetic mice, and not in nondiabetic mice. Finally, control of blood glucose levels by insulin therapy resulted in improvement of the impaired host protection and Th1-related cytokine synthesis. Our results suggest that the reduced production of Th1-related cytokines and NO account for the hampered host defense against M. tuberculosis infection under diabetic conditions.
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PMID:Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with Mycobacterium tuberculosis. 1560 14

The purpose of this study was to determine the effect of the implantation of Taenia solium metacestodes and the treatment with suppressive metacestode factor (F1) on the ability of spleen cells from Balb/c mice to produce cytokines. Cytokine production was estimated 12 days following the implantation or 4 days after the last dose of F1 (five doses) by RT-PCR and flow cytometry analyses. Spleen cells were obtained from metacestode-implanted, F1-treated and control mice. They were stimulated with concanavalin A (ConA) ex vivo and used for RT-PCR studies and for CD25 expression and intracellular cytokine production estimations using specific monoclonal antibodies labeled with phycoerithrin or fluorescein. Results of the RT-PCR showed that all cells expressed IFN-gamma, IL-2 and IL-4 mRNAs. IL-10 mRNA was not expressed in any case. Flow cytometry analyses showed that both spleen CD4+ and CD8+ cells from metacestode-implanted or treated-F1 mice expressed significantly diminished percentages of CD25 when compared with control cells (P<0.05). The estimation of intracellular cytokines showed that the production of IL-2 and IL-4 in CD8+ cells, and of IFN-gamma in CD4+ cells from mice implanted with metacestodes was significantly impaired when compared with the values from control cells (P<0.05).
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PMID:The implantation of Taenia solium metacestodes in mice induces down-modulation of T-cell proliferation and cytokine production. 1567 53

Bacterial DNA triggers B-cell proliferation and induces immunoglobulin secretion. Chromatin-IgG complexes activate autoreactive B cells by co-engaging B-cell receptor (BCR) and TLR-9, thus suggesting a role for innate signaling in systemic autoimmunity. Spleen cells from lupus prone Palmerston North (PN) mice produce several fold less IL-12p40 than controls in response to CpG-oligodeoxynucleotides (ODNs). Here we show that B cells are primarily responsible for this abnormality. The removal of B cells from PN cultures markedly increased IL-12p40. Moreover, the addition of purified B cells back to PN splenocyte cultures resulted in a B-cell number dependent/ IL-10-mediated suppression of IL-12p40. The B cells were the major source of IL-10. In response to CpG, B cells from several lupus strains produced twice as a much IL-10 as controls, but failed to produce IL-10 when stimulated through BCR or CD40. PN and control mice expressed IL-10R similarly, and the difference in IL-10 secretion remained when anti-IL-10R blocking antibodies were used. IFN-gamma and IL-4 regulated CpG-induced IL-10 secretion in opposite directions. The abnormal IL-10 response in lupus mice was derived from B cells with the marginal zone phenotype, and could be downregulated with inhibitory ODNs. We hypothesize that TLR-9 activated lupus B cells can modulate T-cell mediated inflammatory responses through IL-10 production. Therefore, B cells may contribute to the lupus pathogenesis in many different ways: as antigen-presenting cells for self antigens, as effector cells for autoantibody production, and as IL-10 secreting regulatory cells.
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PMID:TLR-9 activation of marginal zone B cells in lupus mice regulates immunity through increased IL-10 production. 1574 55

Despite the recognized role of the T-bet transcription factor in the differentiation of Th1 cells, T-bet-deficient mice can develop small numbers of IFN-gamma-producing CD4 T cells. Although these are not sufficient to allow normal handling of some pathogens, T-bet-deficient mice do resolve infection with the intracellular pathogen Listeria monocytogenes. In contrast, we report that expression of T-bet is required for resistance to Salmonella infection. T-bet-deficient mice succumbed to infection with attenuated Salmonella and did not generate IFN-gamma-producing CD4 T cells or isotype-switched Salmonella-specific Ab responses. Spleen cells from Salmonella-infected T-bet-deficient mice secreted increased levels of IL-10, but not IL-4, upon in vitro restimulation. A Salmonella-specific TCR transgenic adoptive transfer system was used to further define the involvement of T-bet expression in the development of Salmonella-specific Th1 cells. Wild-type Salmonella-specific CD4 T cells activated in T-bet-deficient recipient mice displayed no defect in clonal expansion, contraction, or IFN-gamma production. In contrast, T-bet-deficient, Salmonella-specific CD4 T cells activated in wild-type recipient mice produced less IFN-gamma and more IL-2 upon in vivo restimulation. Therefore, expression of T-bet by CD4 T cells is required for the development of Salmonella-specific Th1 cells, regulation of IL-10 production, and resistance to Salmonella infection.
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PMID:Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. 1617 5

DNA vaccination has emerged as a powerful approach in the search for a more efficacious vaccine against tuberculosis (TB). In this study, we evaluated the immunogenicity and protective efficacy of Mtb8.4/hIL-12 chimeric gene vaccine. The Mtb8.4/hIL-12 chimeric gene was amplified by PCR and cloned into the eukaryotic expression vector pCI-neo. C57BL/6N mice were vaccinated with Mtb8.4/hIL-12 chimeric gene vaccine for three times at 3 weeks intervals. Four weeks after the final inoculation, three mice per group were sacrificed to assess cytokine response and CTL induction and the other five mice per group were challenged intravenously in a lateral tail vein with 1 x 10(6) CFU of virulent Mycobacterium tuberculosis H37Rv. Spleen and the left lung were harvested from each mouse at 4 weeks after infection and homogenized in sterile saline. Serial dilutions of organ homogenates were plated on L-J agar and incubated 37 degrees C until colonies were visible 4 weeks later. Protective efficacies in each experiment were expressed as reduced CFU and were compared with the negative control group. The right lung was obtained from each mouse and immediately inflated with and stored in 10% formalin saline. Tissues were embedded in paraffin, sectioned and stained with hematoxylin and eosin. Mtb8.4/hIL-12 chimeric gene vaccine induced the secretion of more of Th1 cytokines, but not IL-4 and enhanced CTL activity. Mice immunized with Mtb8.4/hIL-12 chimeric gene vaccine had fewer and smaller tubercles than control groups. As expected, control mice had the highest bacterial loads in both lung and spleen. Immunization with Mtb8.4/hIL-12 chimeric gene vaccine could remarkably reduced CFU counts in organs. When it was used to construct the chimeric gene vaccine, hIL-12 could improve the immune efficacy of Mtb8.4 gene vaccine.
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PMID:The immunogenicity and protective efficacy of Mtb8.4/hIL-12 chimeric gene vaccine. 1621 97

Saliva of sand flies (Diptera: Phlebotominae) plays an important role in transmission of Leishmania parasites by modulating host immune response. However, because of the different protein compositions of saliva, the immunomodulatory effects may vary among sand fly species. We have therefore analysed and compared the immunomodulation effects of salivary gland lysate (SGL) of three different sand flies. Spleen cells from BALB/c mice were incubated with SGL of Phlebotomus papatasi, P. sergenti or Lutzomyia longipalpis. Concanavalin A-stimulated lymphocyte proliferation was significantly suppressed with SGLs of all three sand fly species and all SGL doses tested. This result indicates that saliva from different sand fly species is able to suppress host proliferative response even to the potent mitogen. In parallel experiments, we analysed the effect of SGL on IFN-gamma, IL-2, and IL-4 production; in mitogen-stimulated cells SGLs markedly inhibited IFN-gamma production in all intervals tested (reduced up to 31%) and to a lesser degree impaired production of the other two cytokines as well. Despite some species-specific differences in the intensity of immunomodulatory effects, saliva of all sand fly species modulated cell proliferation as well as cytokine production in a similar way.
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PMID:Modulation of murine cellular immune response and cytokine production by salivary gland lysate of three sand fly species. 1625 46

Common helminth infections promote Th2-skewed immune responses in their hosts. We have studied the role of intact carbohydrate structures on Taenia crassiceps compounds in the induction of biased type 2 and anti-inflammatory immune responses on peptide-stimulated T cells by using DO11.10 transgenic (OVA Tg) mice. While OVA Tg mice co-injected with OVA peptide (323-339) (OVA(323-339)) plus intact Taenia soluble antigens (iTSA) displayed significantly higher titers of OVA-specific IgG1 and total IgE, low amounts of these antibodies were detectable in sera from OVA Tg mice co-injected with OVA(323-339) plus periodate-carbohydrate altered TSA (paTSA). Spleen cells from OVA Tg mice failed to efficiently produce OVA-specific IFN-gamma but displayed higher IL-4, IL-5 and IL-10 production when they received OVA(323-339) plus iTSA, compared with OVA Tg mice similarly co-injected with OVA(323-339) plus paTSA. Moreover, after in vivo stimulation with OVA(323-339) plus iTSA, spleen cells did show elevated mRNA transcripts for Arginase 1, Ym1, IL-4, IL-10, TGF-beta, and Mannose Receptor (MR) genes, all them associated with Th2-type and anti-inflammatory responses. Similar results were obtained using TLR4 mutant mice. Together these findings suggest that carbohydrate components in TSA are involved in modulating immune responses to bystander antigens and that do not signal via TLR4.
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PMID:Carbohydrate components of Taenia crassiceps metacestodes display Th2-adjuvant and anti-inflammatory properties when co-injected with bystander antigen. 1659 70

A growing body of evidence indicates that megakaryocytes (MK) or their growth factors play a role in skeletal homeostasis. We previously identified a novel regulatory pathway that controls bone formation, which is mediated by MK. In vivo megakaryocytosis resulted in massive bone formation. The co-culture of MK with osteoblasts (OB) resulted in increased OB proliferation in vitro, by a mechanism that required direct cell-to-cell contact. Here, we examined a second MK-mediated pathway that regulates osteoclast (OC) development. We have begun examining the unique inhibitory effect of MK on OC development. Spleen or bone marrow (BM) cells from C57BL/6 mice, as a source of OC precursors, were cultured with M-CSF and RANKL to induce OC development. MK were prepared by culturing fetal liver cells with thrombopoietin and separating cells into MK and non-MK populations. MK were titrated into spleen cell cultures and OC were identified as tartrate-resistant acid phosphatase-positive giant cells with >3 nuclei. There was a significant, P < 0.001, up to 10-fold reduction in OC formed when MK were added to the spleen cell cultures. We determined that 30% (vol:vol) MK conditioned media (CM) were able to completely block OC development from precursors, whereas 3% MK CM resulted in up to a 10-fold reduction in OC development, P < 0.001. These data indicate that a soluble factor(s) was responsible, at least in part, for the inhibition. We examined MK CM for known inhibitors of OC formation, using ELISAs. IL-4 was undetectable in MK CM, whereas IL-10 and IFN-gamma levels were similar in MK and non-MK CM. TGFbeta-1 levels were increased 2-fold in MK CM compared to control CM but were not responsible for the inhibition in OC development. Although, we found a significant increase in the levels of osteoprotegerin (OPG) in MK CM, antibody neutralization studies, MK derived from OPG-deficient mice, and tandem mass spectrophotometry, all confirm that OPG was not responsible for the MK-mediated inhibition of OC development. Overall, these data suggest that an unidentified factor(s) is present in MK CM that inhibits OC development. These studies indicate that MK can play a dual role in skeletal homeostasis by stimulating OB proliferation and simultaneously inhibiting OC development.
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PMID:Megakaryocyte-mediated inhibition of osteoclast development. 1678 18


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