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

Recent studies indicate that egg granuloma formation in murine Schistosoma mansoni infection is associated with Th2-mediated immune responses. The present study was designed to analyze dynamically the Th1 and Th2 responses in S. japonicum-infected animals and compare them with the results seen with S. mansoni. C3H mice were infected with 10 to 20 cercariae of S. japonicum and sacrificed 3 to 22 weeks later. Spleen cells were stimulated with parasite antigens (egg and adult worm) or the mitogen concanavalin A. Interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon (IFN-gamma) levels were measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA) or bioassays. Additionally, cytokine-producing cells were enumerated by ELISPOT. The results show that Th2 cytokine production, characterized by IL-4 and IL-5, represents the major response in the first month after egg laying begins, while the Th1 functions of IFN-gamma and IL-2 production are greatly depressed. However, by 22 weeks Th2 responses have diminished and IFN-gamma production in response to concanavalin A is apparent. IL-2 responses are minimal at all times. In vitro depletion of T-cell subsets indicates that CD4+ cells are the major subset responsible for production of IL-5 at 7 weeks of infection. These findings suggest that, as in the case of S. mansoni infection, S. japonicum-induced immunopathology is temporally associated with the host Th2 response, although other experiments indicate that IFN-gamma is also involved.
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PMID:Dynamic analysis of splenic Th1 and Th2 lymphocyte functions in mice infected with Schistosoma japonicum. 167 41

The effects of simultaneous administrations of Cyclosporin A (CsA) and Glyburide on the immune system of rats has been evaluated in terms of Interleukin-2 (IL-2) production by Concanavalin A (ConA) stimulated splenocytes and exogenous IL-2 binding capacity. The inhibitory effect of Cyclosporin A on IL-2 production of lymphoid cells is well known. Spleen cells from rats receiving CsA had reduced levels of IL-2 when compared to untreated controls or rats receiving Glyburide only. Splenocytes from rats receiving both drugs had reduced levels of IL-2 when they were sacrificed 24 hours after one or three CsA administrations; instead when the animals were sacrificed 6 days after three CsA administrations, their ability of producing IL-2 is increased as well as increasing exogenous IL-2 binding capacity. These findings let us hypothesize that when there are lower concentrations of CsA in lymphocytes there is an increase of cellular metabolism induced by Glyburide that leads to an increase in IL-2 secretion and in IL-2 receptor expression on cellular surface restoring these levels to normal or slightly above normal levels.
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PMID:Effects of glyburide-cyclosporin A interaction on interleukin-2 production in rats. 1046 81

Hepatocellular carcinoma remains a disease with a poor and dismal prognosis, and all forms of currently available conventional therapies are rarely beneficial. However, in recent years, combined targeting locoregional immunochemotherapy has been reported with very promising results. Adoptive immunotherapy with LAK cells (lymphokine-activated killer cells) and recombinant interleukin-2 is becoming one of the new modalities to reconstitute the depressed immune status of the tumor-bearing host. Interleukin-2, gamma-interferon, and interleukin-12 induce cytolytic activity of LAK and natural killer cells and are considered for cellular activation to locoregional immunotherapy before, after resection or even in unresectable hepatocellular carcinomas. Spleen is a suitable organ for LAK cell induction because it has densely packed lymphocytes. The strategy of administration of both interleukin-2 and gamma-interferon into the spleen for in vivo immunostimulation is based on the well-known synergism of the above cytokines. LAK cells have cytotoxic activity against a variety of tumor cells. In particular, LAK cells exhibit efficacy against lung and liver malignant lesions, as suggested by their trafficking pattern; activated killer cells injected i.v. into humans appeared in the lung early and were subsequently rapidly redistributed to the liver and spleen. Lipiodol-Urografin emulsion is probably an ideal cytokine/anti-cancer drug carrier suitable for the combined locoregional immunochemotherapy because during its preferential retention in the vascular network of the spleen and tumor, a gradual release of both immuno- and chemotherapeutical drugs bound to emulsion droplets is achieved ensuring a prolong half life for these drugs. Recent data point to the potential of considering intratumoral or intravascular use of adenovirus carrying interleukin-12 gene, and/or p53-based gene therapy as possible therapeutic strategies in patients with hepatocellular carcinoma.
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PMID:Locoregional immunochemotherapy in hepatocellular carcinoma. 1214 14

Foxp3(+)CD25(+)CD4(+) regulatory T cells are produced in the thymus (natural T regs) but can also differentiate from peripheral Foxp3(-)CD4(+) precursors (induced or adaptive T regs). We assessed antigen presenting cell (APC) requirements for the latter differentiation. With added transforming growth factor (TGF)-beta, both immature and mature populations of dendritic cells (DCs) induced antigen-specific Foxp3(+) T regs from Foxp3(-) precursors. Using endogenous TGF-beta, DCs from gut-associated mesenteric lymph nodes were capable of differentiating Foxp3(+)T regs. Spleen DCs were 100-fold more potent than DC-depleted APCs for the induction of T regs and required 10-fold lower doses of peptide antigen. Interleukin-2 (IL-2) was essential, but could be provided endogenously by T cells stimulated by DCs, but not other APCs. The required IL-2 was induced by DCs that expressed CD80/CD86 costimulatory molecules. The DC-induced Foxp3(+)T regs divided up to 6 times in 6 days and were comprised of CD62L and CD103 positive and negative forms. The induced Foxp3(+)T regs exerted suppression in vitro and blocked tumor immunity in vivo. These results indicate that DCs are specialized to differentiate functional peripheral Foxp3(+)T regs and help set the stage to use DCs to actively suppress the immune response in an antigen-specific manner.
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PMID:Dendritic cells are specialized accessory cells along with TGF- for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3 precursors. 1769 44

Many cancer types carry mutations in protein tyrosine kinase (PTK) and such alterations frequently drive tumor progression. One category is gene translocation of PTKs yielding chimeric proteins with transforming capacity. In this study, we characterized the role of ITK-FER [Interleukin-2-inducible T-cell Kinase (ITK) gene fused with Feline Encephalitis Virus-Related kinase (FER) gene] and ITK-SYK [Interleukin-2-inducible T-cell Kinase (ITK) gene fused with the Spleen Tyrosine Kinase (SYK)] in Peripheral T Cell Lymphoma (PTCL) signaling. We observed an induction of tyrosine phosphorylation events in the presence of both ITK-FER and ITK-SYK. The downstream targets of ITK-FER and ITK-SYK were explored and STAT3 was found to be highly phosphorylated by these fusion kinases. In addition, the CD69 T-cell activation marker was significantly elevated. Apart from tyrosine kinase inhibitors acting directly on the fusions, we believe that drugs acting on downstream targets could serve as alternative cancer therapies for fusion PTKs.
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PMID:Translocation-generated ITK-FER and ITK-SYK fusions induce STAT3 phosphorylation and CD69 expression. 3021 47