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)

In the presence of interferon-gamma (IFN-gamma), human tumor necrosis factor-alpha (Hu-TNF-alpha), which binds to murine TNF-alpha receptor type 1 (TNF-R1) but not to murine TNF-R2, was effective in inducing nitric oxide (NO) production in spleen-derived macrophages (M phi), albeit at concentrations 12.5-fold greater than those required by murine TNF-alpha (Mu-TNF-alpha), to achieve the same result. Addition of anti-TNF-R1 completely inhibited the Mu-TNF-alpha-mediated induction of NO, demonstrating that TNF-R1 is critical to the IFN-gamma-dependent TNF-alpha-mediated induction of M phi effector function. However, treatment with anti-TNF-R2 resulted in a partial inhibition of M phi activation. Spleen-derived M phi were more dependent on TNF-R2 than RAW 264.7 or peritoneal M phi based on their responsiveness to Hu-TNF-alpha. Priming of spleen-derived M phi with either IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF) heightened the maximal responses to both TNF-alpha species and increased the overall effectiveness of Hu-TNF-alpha without increasing expression of either TNF-alpha receptor. The dependence of spleen-derived M phi on both TNF-alpha receptors for signaling the induction of effector function supports an active signaling role for TNF-R2 in its synergy with TNF-R1 rather than a passive ligand passing role.
J Interferon Cytokine Res 1996 Dec
PMID:Cytokine priming reduces dependence on TNF-R2 for TNF-alpha-mediated induction of macrophage nitric oxide generation. 897 9

We investigated the production of IL-2 and IFN-gamma (Th1 type) and IL-4 (Th2 type) cytokines by mitogen-activated spleen cells from young, adult and old mice. Cytokine production was evaluated in culture supernatants by CTLL proliferation (IL-2), ELISA (IFN-gamma), CT4.S proliferation (IL-4) and in mRNA extracted from activated CD4+ cells by RT-PCR (IL-2, IFN-gamma and IL-4). Results show that the production of IL-2, as protein and mRNA, is profoundly depressed by aging, whereas that of IFN-gamma, as protein and mRNA, firstly declines and then increases with age. The production of IL-4, as protein, monotonically declines with aging whereas, as mRNA, firstly decreases and then increases above the level in young mice. Spleen cells in culture were also incubated with mitogens and with a recombinant cytokine (IL-1 beta, IL-2, IL-3, IL-4, IL-12 or IFN-gamma) at various concentrations. It was found that recombinant cytokines by and large enhance cytokine production when the level induced by mitogens only is low. This conclusion applies to IL-2 and IFN-gamma production as protein and mRNA. The addition of recombinant cytokines also increases the production of IL-4 at the protein level in spleen cells from old mice but, at the mRNA level, only in spleen cells from young mice. This finding suggests age-related changes in IL-4-specific mRNA transcription rate and post-transcriptional half-life as well as translation kinetics.
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PMID:Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. 908 80

Specific and non-specific parasite-induced changes in lymphocyte responses were analysed in C57/BL/6J mice after intrahepatic infection with Echinococcus multilocularis. Spleen cells harvested at selected times after infection were in vitro stimulated with mitogens or a crude soluble parasite extract (EmAg) at an optimized dose. Cell proliferative responses to Con-A were not modified by the infection over the first 22 weeks. In contrast, LPS-induced responses were decreased from the 13th week. A strong CD4+ proliferative T-cell response to the parasitic extract of infected mouse spleen cells was observed at the early stage of infection. This response then progressively decreased but remained significantly higher than that of control mice until the 19th week of infection. Cytokine production was investigated after in vitro EmAg stimulation of spleen cells. IFN-gamma, IL-2, IL-5 were produced within the first weeks after infection whereas the detection of IL-10 was slightly delayed. Thus, the promotion of the disease does not appear associated with the expansion of one rather than another T-cell subset in C57BL/6J mice. A general immunosuppression affecting both mitogenic and parasite-specific T-cell responses was observed at the end of the infection.
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PMID:Characterization of T-cell immune responses of Echinococcus multilocularis-infected C57BL/6J mice. 922 82

The role of antigen-presenting cells (APC) in regulating the balance of T helper type 1 (Th1) and T helper type 2 (Th2) responses and cytokine production is unclear. Dendritic cells (DC), the most potent APC for naive T cell activation, were found to regulate Th1 and Th2 cytokine profiles in a manner dependent on their tissue of origin. Using whole tissues or purified cell mixtures, spleen (systemic) DC were found to induce mainly Th1 cytokines, and Peyer's patch (mucosal) DC were found to induce predominantly Th2 cytokines. Spleen DC induced high levels of interferon-gamma (IFN-gamma) or interleukin-2 (IL-2) or both, and Peyer's patch DC induced IL-4 or IL-6 or both in spleen and Peyer's patch T cells, allogeneic mixed leukocyte reactions, or antigen-specific Th0 clones. These data suggest that the tissue of origin of DC has a significant impact on subsequent T cell development.
J Interferon Cytokine Res 1998 Feb
PMID:Dendritic cells from Peyer's patch and spleen induce different T helper cell responses. 950 61

Previous studies have described an oral influenza vaccine comprising whole irradiated virus and an erythrocyte complex (IV-EC), which gave broad-based protection against influenza virus challenge in mice. The present study examined the immune responses generated after live virus challenge of vaccinated mice, particularly to determine whether mice vaccinated with IV-EC had enhanced CTL activity to compensate for the previously reported diminution in lung IgA response. Oral vaccine groups examined were IV-EC, live virus alone (LV) or live virus-erythrocyte complex (LV-EC), compared with irradiated virus and erythrocyte alone controls. The antibody responses of IV-EC and LV-EC vaccinated mice showed significantly elevated lung and serum IgG2a levels post live virus challenge, with no comparable increases in IgG1 levels compared to controls. Spleen cells from IV-EC mice showed an enhanced post-challenge proliferative response to antigen compared with mice that had received live oral vaccines, indicating enhanced cellular activity post IV-EC immunization. However, CTL activity was not enhanced for IV-EC mice, and live virus-vaccinated mice had reduced CTL activity compared with controls, indicating that CTL were not important for post-vaccine protection. Cytokine analysis revealed a predominant IFN-gamma response in spleen cells from orally vaccinated mice, whereas IL-4 was not detected in any lung or spleen culture analysed. The results suggest, therefore, that protection from live influenza challenge after IV-EC or LV-EC vaccination was due to an IFN-mediated IgG2a response. Definitive confirmation of the role of these factors in post-vaccine protection can now be tested in IgG2a-depleted or IFN-gamma gene knockout mouse models.
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PMID:Studies on the IgA-independent immunological responses in mice to influenza virus challenge after oral vaccination with irradiated whole virus and an erythrocyte complex. 1076 15

We analyzed differential responses of spleen and liver, major organ targets for viscerotropic Leishmania species, to experimental infection and examined if resistance to challenge was organ-specific. In liver, parasites were spontaneously cleared and iNOS trancripts expression paralleled that of amastigote load. In the spleen, amastigote multiplication was only partly controlled, and iNOS transcripts expression was transient. Total numbers of spleen cells, B cells, and T cells were decreased, while F4/80(+) and Mac1(+) cells were conserved. Expression of splenic MCP-1 transcripts remained constant, indicating its possible contribution to immigration of Leishmania host cells and to sustained parasite load. Spleen cells produced both, Th1- and Th2-type cytokines and Th2-type response was dominant, compatible with the sustained MCP-1 expression. Challenge experiments showed that in contrast to the liver, where initial infection conferred a progressively established immunity, in the spleen there was no induced protection against reinfection. Organ-specific resistance against challenge could be important for designing antileishmanial vaccines.
Eur Cytokine Netw
PMID:Sustained parasite burden in the spleen of Leishmania infantum-infected BALB/c mice is accompanied by expression of MCP-1 transcripts and lack of protection against challenge. 1139 24

There is a large amount of evidence describing the expression, interaction, and mode of activation of the human interferon (IFN)-mediated double-stranded RNA-activated protein kinase (PKR) gene. Studies from Pkr-null mice have defined the kinase as a transducer of dsRNA signals that converge on transcription, translation, and apoptotic programs involved in the innate resistance to viral infection. In vitro studies also suggest that PKR may possess important cell growth regulatory and tumor suppressor properties. However, the study of Pkr-null mice has not fully elucidated the role that the kinase plays in these processes, in part because of apparent redundancies in PKR-dependent and PKR-independent regulatory pathways. To overcome such limitations and to begin to examine the role of PKR in a complex biologic system, we have generated transgenic mice overexpressing wild-type human (Hu) PKR. HuPKR was expressed and active in various tissues and associated with a small body phenotype. Spleen cells from transgenic mice were resistant to apoptosis when treated with the genotoxic agent actinomycin D and showed a decrease in proliferation in response to concanavalin A (ConA) compared with spleen cells from wild-type control mice. The initial characterization of this transgenic mouse line suggests it may be useful as a model for investigating biology and diseases relative to a number of scientific disciplines.
J Interferon Cytokine Res 2002 Mar
PMID:Expression of human PKR protein kinase in transgenic mice. 1203 40

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

Citrobacter rodentium induces an acute, self-limited colitis in mice which is histologically associated with crypt hyperplasia. The infection serves as a model for human infectious colitis induced by enteropathogenic Escherichia coli. We investigated if Balb/c mice, which had spontaneously cleared C. rodentium infection, were protected against re-infection and if resistance against intestinal infection can be systemically transferred using spleen cells. The course of infection was monitored by faecal excretion. Spleen cells, splenic CD3+ and CD4+ cells were transferred from resistant mice to non-infected recipients prior to infection. Cytokine secretion, serum and faecal antibody titres and histological disease severity were assessed. Balb/c mice were resistant against re-infection. The course of infection was shorter in mice receiving primed spleen cells, CD3+ and CD4+ cells. Transfer of CD4+ T cells from resistant mice induced gamma-interferon, interleukin (IL)-2 and IL-17 secretion and suppressed IL-10 secretion. Anti-Citrobacter serum IgG1 and IgG2a enzyme-linked immunosorbent assay OD levels were increased. Faecal IgA secretion was increased while serum IgA was suppressed in recipients of CD4+ cells. Large bowel histology showed protection from colitis in recipients of primed cells as indicated by normal colonic epithelium. In Balb/c mice, C. rodentium infection is followed by resistance, which can be transferred by CD4+ cells. Transfer of protection is associated with IL-17 secretion, enhanced serum IgG and faecal IgA secretion. This is the first study to demonstrate the mechanisms by which systemic resistance from previously C. rodentium-infected mice can be transferred to non-infected animals.
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PMID:CD4+ T cells transfer resistance against Citrobacter rodentium-induced infectious colitis by induction of Th 1 immunity. 1826 Oct 38

Elevated levels of glucose and free fatty acids as well as changes in the cytokine production are common features of both type 1 and type 2 diabetes. Especially regarding type 1 diabetes, immunological factors are believed to be responsible for much of the disease pathology. The aim of this study was to investigate whether the diabetic environment in itself could affect cytokine production. Spleen cells from normal mice were cultured for 96 h with addition of different concentrations of glucose (2.8, 5.6, 11.1, 28 mM) or the free fatty acid palmitate (50-100 microM). Cytokine supernatant secretions and mRNA expressions were determined. The cytokine production was highest in cells cultured at 11.1mM glucose. TNFalpha and IFNgamma secretion was decreased by high glucose. Palmitate and/or the ethanol used to dissolve it had a suppressive effect on the secretion of all the investigated cytokines. This effect was counteracted by an elevated glucose concentration for TNFalpha and IFNgamma, but not IL-10. In conclusion, our data suggest that metabolic aberrations characterizing a diabetic environment can have a direct impact on cytokine production by immune cells.
Cytokine 2008 Jul
PMID:Effects of a diabetes-like environment in vitro on cytokine production by mouse splenocytes. 1845 22


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