Forskolin potentiates G-CSF-induced proliferation of a murine myeloblastic leukemia cell line.
The role of the cAMP/A-kinase signaling pathway in G-CSF dependent proliferation of murine myeloblastic NFS-60 cells was investigated. G-CSF treatment resulted in a rapid and transient elevation of cAMP content of NFS-60 cells. G-CSF treatment of NFS-60 cells also resulted in the activation of A-kinase parallel to the increase in cAMP concentration. A low concentration (0.2-10 nM) of forskolin augmented the G-CSF-dependent cell proliferation, although forskolin by itself had no effect on NFS-60 cell growth. Forskolin did not affect the IL-3-induced proliferation of this cell line. Addition of forskolin resulted in further increases in the cAMP level, activation of A-kinase in NFS-60 cells stimulated by G-CSF. Proliferation of NFS-60 cells by G-CSF, but not by IL-3, was blocked by the axial diastereoisomer of adenosine 3',5'-phosphorothioate (Rp-cAMPS), a competitive cAMP antagonist. KT-5720(8R*,9S*,11S*)-(-)-9-hydroxy-9-n-hexyloxy-8-methyl-2, 3, 9, 10-tetrahydro-8, 11-epoxy-1H, 8H, 11H-2,7b, 11a-triazadibenzo(a,g) cycloocta(c,d,e)trinden-1-one), an A-kinase inhibitor, inhibited the G-CSF-dependent proliferation. These findings suggest that activation of the cAMP/A-kinase signaling pathway may be involved in G-CSF-mediated cell proliferation of NFS-60 cells, whereas IL-3-dependent proliferation is not mediated in such a manner.
Kobayashi
K
K
Department of Internal Medicine, Mie University School of Medicine, Japan.
Nishikawa
M
M
Omay
S B
SB
Toyoda
H
H
Deguchi
K
K
Shirakawa
S
S
D000818:Animals; D002227:Carbazoles; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D004357:Drug Synergism; D004789:Enzyme Activation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000378:metabolism / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D002227:Carbazoles; D007211:Indoles; D007377:Interleukin-3; D011758:Pyrroles; D016179:Granulocyte Colony-Stimulating Factor; D005576:Colforsin; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases