Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) infection was studied in two different human neuroblastoma cell lines, SK-N-MC and SH-SY5Y. Results from immunofluorescence analysis indicate that SK-N-MC cells express a 68K neurofilament, and SH-SY5Y cells express additionally a 160K to 200K neurofilament complex and thus represent a more differentiated state. HIV-1 infection in these cell lines was demonstrated by nested polymerase chain reaction and further characterized by in situ hybridization, which showed that about 50% of SK-N-MC cells and 20% of SH-SY5Y cells were infected by HIV-1 and contained integrated proviral HIV-1 DNA. Among the cytokines and growth factors studied, tumour necrosis factor alpha (TNF-alpha) enhanced virus production in both cell lines, but to a differing extent, according to our mRNA and p24 antigen capture assay. In SK-N-MC cells the enhancement of HIV-1 mRNA was detected after 24 h of stimulation, and declined to the control level by 48 h. In SH-SY5Y cells a clear-cut stimulation was seen at both time points. By contrast, interleukin-6 (IL-6) enhanced the virus replication only in SK-N-MC cells, as shown at the mRNA level. Immunochemical staining showed no differences in the proportion of HIV-1-positive cells after 48 h of stimulation by TNF-alpha or IL-6 when compared to the control cells. In addition, based on a thymidine incorporation assay, TNF-alpha inhibited, but IL-6 strongly increased, the DNA synthesis in SK-N-MC cells, whereas in the SH-SY5Y cell line no such differences were seen. We discuss the possibility that developing, less-differentiated neurons may be more readily infected by HIV-1 than fully differentiated neurons, and that cytokines such as TNF-alpha and IL-6, which are elevated in HIV-1-infected individuals, may enhance HIV production.
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PMID:Activation of integrated human immunodeficiency virus type 1 in human neuroblastoma cells by the cytokines tumour necrosis factor alpha and interleukin-6. 162

Human immunodeficiency virus type 1 (HIV-1)-associated central nervous system disorders, including encephalopathy, often occur in the late stage of HIV-1 infection. Some inflammatory cytokines and HIV-1 antigens released from infected microglia or brain macrophages are considered to play an important role in neuropathogenesis. In this study, an in vitro assay system has been established for the evaluation of neural cell death, which would be predictive of the pathogenesis of neural cell death in vivo. The human neuroblastoma cell line SK-N-SH was differentiated to a neural phenotype with retinoic acid, while the promyelocytic cell line HL-60 and its HIV-1-infected clone OM-10.1 were differentiated to macrophages with phorbol myristate acetate. When neural (differentiated SK-N-SH) cells were cocultured with either uninfected or HIV-1-infected macrophages (differentiated HL-60 or OM-10.1 cells, respectively) for 3-5 days, significant neural cell death was observed in the cells cocultured with infected macrophages. Direct contact with macrophages was not necessary for the induction of neural cell death, since indirect coculture or coculture supernatants could also induce neural cell death. Large amounts of cytokines and chemokines were released in the coculture supernatants. The CXCR4 antagonist AMD3100 and the HIV-1 transcription inhibitor K-37 partially inhibited neural cell death. These results indicate that this system seems to be a useful tool for the evaluation of compounds against HIV-1-induced neural cell death.
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PMID:Establishment of an in vitro assay system mimicking human immunodeficiency virus type 1-induced neural cell death and evaluation of inhibitors thereof. 1260 87