PMID- 7510778 OWN - NLM STAT- MEDLINE DCOM- 19940420 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 62 IP - 4 DP - 1994 Apr TI - Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and interleukin-6 but not TNF-beta induce differentiation of neuroblastoma cells: the role of nitric oxide. PG - 1330-6 AB - Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6), but not TNF-beta, can induce the in vitro differentiation of the neuroblastoma cell line N103 in a dose-dependent manner. Differentiation of N103 was accompanied by the arrest of cell growth and neurite formation. The induction of neuroblastoma cell differentiation by TNF-alpha and IFN-gamma can be specifically inhibited by a nitric oxide (NO) synthase inhibitor, L-NG-monomethylarginine. In contrast, the differentiation of N103 cells by IL-6 was not affected by L-NG-monomethylarginine. These results indicate that TNF-alpha and IFN-gamma, but not IL-6, induce the differentiation of neuroblastoma cells via NO. This is confirmed by the finding that the culture supernatants of N103 cells induced by TNF-alpha and IFN-gamma, but not that by IL-6, contained high levels of NO2-, the production of which was inhibited by L-NG-monomethylarginine. Furthermore, the differentiation of N103 cells can be induced directly in a dose-dependent manner by the addition of nitroprusside, a generator of NO, into the culture medium. These data therefore indicate that NO may be an important mediator in the induction of neuronal cell differentiation by certain cytokines such as TNF-alpha and IFN-gamma and that neuronal cells, in addition to the macrophage-like brain cells, can be induced by immunological stimuli to produce large quantities of NO. FAU - Munoz-Fernandez, M A AU - Munoz-Fernandez MA AD - Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autonoma de Madrid, Spain. FAU - Cano, E AU - Cano E FAU - O'Donnell, C A AU - O'Donnell CA FAU - Doyle, J AU - Doyle J FAU - Liew, F Y AU - Liew FY FAU - Fresno, M AU - Fresno M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Interleukin-6) RN - 0 (Lymphotoxin-alpha) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 27JT06E6GR (omega-N-Methylarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) RN - 9007-49-2 (DNA) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.4.- (Amino Acid Oxidoreductases) SB - IM MH - Amino Acid Oxidoreductases/antagonists & inhibitors MH - Animals MH - Arginine/analogs & derivatives/pharmacology MH - *Cell Differentiation MH - DNA/biosynthesis MH - Interferon-gamma/*pharmacology MH - Interleukin-6/*pharmacology MH - Lymphotoxin-alpha/pharmacology MH - Mice MH - Neuroblastoma/*pathology MH - Nitric Oxide/*physiology MH - Nitric Oxide Synthase MH - Recombinant Proteins/pharmacology MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology MH - omega-N-Methylarginine EDAT- 1994/04/01 00:00 MHDA- 1994/04/01 00:01 CRDT- 1994/04/01 00:00 PHST- 1994/04/01 00:00 [pubmed] PHST- 1994/04/01 00:01 [medline] PHST- 1994/04/01 00:00 [entrez] AID - 10.1046/j.1471-4159.1994.62041330.x [doi] PST - ppublish SO - J Neurochem. 1994 Apr;62(4):1330-6. doi: 10.1046/j.1471-4159.1994.62041330.x.