Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 15 (IL-15) is an important regulatory cytokine in cellular immunity. In vitro replacement of IL-15 has been shown to enhance immunity in Human immunodeficiency virus type 1 (HIV-1) infected lymphocytes. We evaluated the effect of IL-15 on the survival of peripheral blood mononuclear cells of HIV patients by examining in vitro lymphocyte apoptosis, and correlated the process with Bcl-2 and Fas gene regulation. Peripheral blood mononuclear cells (PBMC) from 21 HIV-infected adults and 24 HIV-seronegative healthy individuals were isolated and cultured to determine the effect of escalating doses of IL-15 (0, 1, 10, 100, 1000 ng/mL) on apoptosis. Lymphocyte proliferation assay with (3H) TdR was measured and Bcl-2 and Fas gene regulation was observed. The results were as follows: 1) IL-15 reduced culture induced lymphocyte apoptosis in HIV patients in a dose dependent manner, and reached a plateau level at a concentration of 100 ng/ml; 2) IL-15 significantly reduced the level of apoptosis after 3 days (14%) and 5 days (15%) of culture in HIV patients, while no difference was observed in HIV (-) donors; 3) The percentage of viable cells among the total number of lymphocytes was significantly enhanced by 25% in HIV patients with IL-15; 4) Bcl-2 expression was decreased in HIV patients (53.9 +/- 12.3%) compared to HIV (-) donors (93.0 +/- 3.7%), and IL-15 increased Bcl-2 expression by 21.2 +/- 5.2% in HIV patients; 5) Fas expression was increased in HIV patients (70.2 +/- 4.6%) compared to HIV (-) donors (32.4 +/- 4.3%), and IL-15 increased Fas expression by 8.4 +/- 1.2% in HIV (-) donors. Our findings indicate that IL-15 may influence immunologic abnormalities in HIV infection, particularly its ability to prevent apoptosis of lymphocytes by suppressing the down-modulation of Bcl-2. This may provide an experimental basis for IL-15 immunotherapy.
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PMID:Spontaneous programmed cell death of peripheral blood mononuclear cells from HIV-infected persons is decreased with interleukin-15. 1073 28

Interleukin 15 (IL-15 mRNA expression was detected in human colorectal cancer cells (Colo320, WiDr, TCO and DLD1) by the reverse transcriptase-polymerase chain reaction (RT-PCR). Only Colo320 and WiDr cells secreted IL-15 culture medium. With IL-15 treatment, all cell lines grew at a rate of 120-180% of that of nontreated cells. A binding assay with (125)I-labeled IL-15 showed binding activity to IL-15 in Colo320 (K(d): 0.098 nM) cells. IL-15 also reversed the growth inhibition caused by serum starvation in Colo320 cells. IL-15-induced cell growth in regular and serum-free media was abrogated by anti-IL-15 antibody treatment in Colo320 cells. Moreover, IL-15 treatment reduced doxorubicin-induced cytostasis and cytolysis in Colo320 cells by 50%. The invasion capacity of IL-15-treated Colo320 cells was 5.3 times that of untreated cells. Immunoblotting showed that IL-15-treated Colo320 cells exhibited downregulation of p21Waf1 and Bax, and upregulation of Bcl-2, phospho-AKT, MMP9/MMP2, and VEGF. Finally, immunostaining of human colon cancer revealed that 33 (70%) of 47 Dukes' C cases showed IL-15 expression in cancer cells, whereas only 16% of Dukes' B cases did (p < 0.0001). IL-15 may play important roles in cell proliferation, invasion, and metastasis of human colorectal cancer.
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PMID:Interleukin-15 expression is associated with malignant potential in colon cancer cells. 1175 2