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)

Infection with Trypanosoma cruzi is accompanied by a profound suppression of immune responses including the production of IL-2. Previous experiments have confirmed a correlated decrease in IL-2 mRNA levels in lymphoid cells from infected mice. To further define the molecular basis of this regulation, we have examined the production and degradation of mRNA for IL-2 and other T cell activation genes in cells from T. cruzi-infected mice. Spleen cells from C57BL/6J mice infected with the Brazil strain of T. cruzi were analyzed for the kinetic expression of IL-2, IL-2R alpha, c-myc, and c-fos genes in response to Con A and PMA costimulation. Cells from infected mice exhibited a selective reduction of c-myc and c-fos mRNA in association with the severe suppression of the IL-2 gene, but a less severe to comparable production of IL-2R alpha mRNA compared with normal spleen cells. The similar patterns of the suppression of c-myc and IL-2 mRNA suggest a common mechanism of down-regulation of these two genes in T. cruzi infection. Actinomycin D treatment was used to demonstrate that decreased steady state levels of IL-2, c-myc, and c-fos mRNA in cells from infected mice were not due to an increased rate of degradation of these mRNA. Cycloheximide treatment enhanced the expression of IL-2, IL-2R alpha, c-myc, and c-fos mRNA in spleen cells from both normal and infected mice. Although a larger percentage of induction was observed in cells from infected mice, the mRNA levels for IL-2, c-myc, and c-fos in cells from infected mice were still lower than those of normal cells. Spleen cells from infected mice precultured for 24 to 72 h before the addition of mitogens showed significant enhancement of IL-2 and c-myc gene expression; however, this recovery was inhibited if fixed T. cruzi was present in the preculture medium. These data suggest that the reduction of IL-2 mRNA in infected mice is not the result of an increased degradation of its mRNA but to down-regulation of transcription of the IL-2 gene in T cells from T. cruzi-infected mice. Preculture-induced recovery of IL-2 production appears to result from release from this regulation and full expression of the IL-2 gene.
 ...
PMID:Selective suppressive effects of Trypanosoma cruzi infection on IL-2, c-myc, and c-fos gene expression. 151 73

C3H 10T1/2 mouse fibroblasts were transfected with a plasmid vector composed of EJ, the mutated c-Ha-ras, and a metallothionein promotor that induced amplified ras expression when activated by culture in the presence of zinc. Experiments were conducted to compare the effect of induction on killing by activated natural killer (NK) cells, cytotoxic T lymphocytes, activated macrophages, and antibody plus complement. The only effector that recognized increased ras expression and exhibited high-inducible cytolysis was an activated NK cell. The effectors from spleen were poly I.C. boostable, Lyt-1.1 negative, NK 1.2 positive, and asialo GM1 positive. Spleen cells from T cell-deficient nude mice, but not NK-deficient beige mice, exhibited high levels of killing activity, and experiments with NK cell clones demonstrated that these lines were also highly cytolytic and killed Ha-ras transfectants in parallel to YAC. Transfection of the same fibroblast line with c-myc did not alter the level of activated NK sensitivity. Cold target competition experiments revealed that Ha-ras-transfected and non-transfected 10T1/2 fibroblasts competed equally for lysis of either YAC or Ha-ras transfectants. Rat-1 fibroblasts did not compete, but gained this capacity when transformed with the v-Ki-ras oncogene but not v-fps. These data suggest that Ha-ras acts in target cells at a post-binding step, whereas Ki-ras may affect expression of target-effector binding structures. The findings that activated NK cell lysis may be specifically influenced by ras expression support a role for NK cells in host surveillance against early neoplastic changes.
 ...
PMID:Enhanced lytic susceptibility of Ha-ras transformants after oncogene induction is specific to activated NK cells. 349 78