Oncostatin M regulates VIP expression in a human neuroblastoma cell line.
Oncostatin-M (OM), a recently described glycoprotein cytokine, is structurally and functionally related to cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) and ciliary neurotrophic factor (CNTF). To determine whether OM, like CDF/LIF and CNTF, possesses trophic or differentiative functions for neurons we examined the effects of recombinant human OM on ciliary neuron survival and neurotransmitter expression in sympathetic neurons. Like CDF/LIF, but in contrast to CNTF, OM had no effect on ciliary neuronal survival at any concentration tested. OM produced small but reproducible increases in choline acetyl transferase (ChAT) activity and vasoactive intestinal peptide (VIP) levels in rat sympathetic neuron cultures, but this effect was significantly less than that of CNTF or CDF/LIF. To determine if human OM would elicit a more robust response from human cells, we utilized a human neuroblastoma cell line, NBFL, that responds to CNTF and CDF/LIF by altering vasoactive intestinal peptide (VIP) levels. OM specifically elevated VIP and c-fos mRNA levels in NBFL cells and was as potent as CDF/LIF in this assay. Our data provides evidence that OM acts on neurons and identifies a neural cell line responsive to OM, CNTF, CDF/LIF.
Rao
M S
MS
Division of Biology, Caltech, Pasadena.
Symes
A
A
Malik
N
N
Shoyab
M
M
Fink
J S
JS
Landis
S C
SC
D000818:Animals; D015152:Blotting, Northern; D002642:Chick Embryo; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007202:Indicators and Reagents; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D011863:Radioimmunoassay; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis*
D006131:Growth Inhibitors; D007202:Indicators and Reagents; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009479:Neuropeptides; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D014660:Vasoactive Intestinal Peptide; D002795:Choline O-Acetyltransferase