Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional immaturity of neonatal T cells is related to their immature phenotype, with the majority of neonatal T cells of naive (CD45RA+) T cells. The progression of T cells from naive cells to effector cells is dependent on the survival of Ag-specific T cells and their resistance to apoptosis. In this study, we showed for the first time that insulin-like growth factor 1 (IGF-1) converted cord blood CD45RA+ T cells to CD45RO+ T cells and inhibited cord blood T cell apoptosis. We found cord blood T cells stimulated with PHA would result in gradual loss of CD45RA and gain of CD45RO expression. IGF-1 further increased the loss of CD45RA and enhanced CD45RO expression in PHA-stimulated cord blood T cells. In addition, IGF-1 prevented cord blood T cells from spontaneous apoptosis through a mechanism other than Fas/FasL. In PHA-activated cord blood T cells, IGF-1 prevented both naive (CD45RA+) and memory/mature (CD45RO+) T cells from apoptosis. Moreover, cord blood T cells cultured with IGF-1 and PHA had a higher resistance to anti-Fas-induced apoptosis as compared with PHA-activated cord blood T cells. IGF-1 also significantly inhibited PHA-induced Fas expression on cord blood T cells. These results demonstrate that IGF-1 promotes the maturation and maintains the survival of cord blood T cells. Its antiapoptotic effect in PHA-activated cord blood T cells may be mediated through the down-regulation of Fas expression.
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PMID:Insulin-like growth factor 1 promotes cord blood T cell maturation and inhibits its spontaneous and phytohemagglutinin-induced apoptosis through different mechanisms. 1090 34

Decreased graft-versus-host disease (GVHD) in cord blood (CB) transplantation may be attributed to the immunological immaturity and susceptibility to apoptosis of CB mononuclear cells (MNCs). Cytokines like interleukin (IL)-12 and IL-15 may be used for in vivoadministration or ex vivo expansion of lymphoid cells for more rapid recovery following stem cell transplant, and for providing a graft-versus-leukemia (GVL) effect. We investigated the effects of IL-12 and IL-15, alone or in combination on apoptosis and proliferation of both CB and adult peripheral blood (APB) MNCs, with particular emphasis on CB CD4+, CD8+ and CD56+ lymphocyte subpopulations. The results of our study indicated that: (1) the combination of IL-12+IL-15 resulted in a greater degree of CB and APB apoptosis than either cytokine alone; (2) the level of both spontaneous and cytokine-induced apoptosis by IL-12 and/or IL-15 are greater in CB MNCs than in APB MNCs using TUNEL assays; (3) IL-15 is superior to IL-12 in enhancing the proliferative response in CB and APB MNCs; (4) the combination of IL-12+IL-15, but not either cytokine alone, significantly enhanced apoptosis in CD8+ and CD56+ CB subsets, but not in CD4+ CB subsets; (5) IL-12 or IL-15 alone resulted in increased proliferation in CD4+, CD8+ and CD56+ CB subsets, with IL-12+IL-15 producing the greatest increase of proliferation in all three CB subsets; and (6) IL-15 and/or IL-12 significantly upregulate Fas (CD95) expression on CB T and NK cells. These findings may have therapeutic implications when designing cytokine therapy in patients receiving CB transplant.
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PMID:Effect of interleukin (IL)-12 and IL-15 on apoptosis and proliferation of umbilical cord blood mononuclear cells. 1159 16

Aging sensitizes the liver to the hepatocarcinogenic effect of PPARalpha agonists via unknown mechanisms. This study was designed to investigate whether aging enhances the susceptibility of the liver to the anti-apoptotic effect of these chemicals. Since apoptosis serves to purge the liver of transformed cells, exaggerated inhibition of this process in aged livers may facilitate the progress of these cells to cancer. We quantified the effect of the PPARalpha agonists, clofibrate and Wy-14643, on the mRNA levels of various elements of the apoptotic machinery in male Fisher-344 rats ranging in age from immaturity (4-week-old), young adulthood (10-week-old), middle age (50-week-old), to senescence (100-week-old). Clofibrate and Wy-14643 either significantly diminished or exerted no effect on hepatic mRNA levels of several pro-apoptotic factors in immature, middle age and senescent animals. Unexpectedly, however, these PPARalpha agonists caused a remarkable 2- to 45-fold augmentation in the levels of the mRNA of Bax, caspase-2, and Fas mRNA in the young adult 10-week-old rats. A 47-75% decrease in the percent of apoptotic hepatocytes was observed only in 50- and 100-week-old rats treated with Wy-14643. Data suggest that activation of PPARalpha alters the balance between pro- and anti-apoptotic genes most significantly in livers of 50- and 100-week-old rats. Since suppression of apoptosis in the senescent liver is expected to diminish its ability to purge itself of already transformed cells, which may then progress to malignancy, exposure of senescent animals to PPARalpha agonists may be crucial to the ultimate outcome of liver cancer later in their life-span.
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PMID:Age-dependent effects of nongenotoxic hepatocarcinogens on liver apoptosis in vivo. 1266 31