Granulocyte colony-stimulating factor directly affects human monocytes and modulates cytokine secretion.
OBJECTIVE
Recent reports have indicated that monocytes express receptors for the granulocyte colony-stimulating factor (G-CSF). The direct effects of G-CSF on cytokine secretion in monocytes were examined.


METHODS
A monocytic cell line NOMO-1 that secretes multiple cytokines upon stimulation with lipopolysaccharide (LPS) was used. Normal human monocytes were purified by negative selection using magnetic beads. Cells pretreated with or without G-CSF were stimulated with LPS, and the subsequent concentrations of cytokines and chemokines in supernatants were determined by sandwich enzyme-linked immunosorbent assay.


RESULTS
NOMO-1 cells were found to express receptors for G-CSF. Although G-CSF stimulation did not induce cytokine secretion, pretreatment with G-CSF significantly attenuated LPS-stimulated secretion of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-12 in NOMO-1 cells. Simultaneously, however, G-CSF pretreatment apparently enhanced LPS-induced secretion of IL-10 and monocyte chemoattractant protein-1, whereas secretions of IL-1beta, IL-6, and IL-8 were unaffected. When normal human monocytes from healthy volunteers were similarly examined, marked individual variations in LPS-induced secretion of cytokines were observed. Although some exceptions exist, a similar tendency as to the effects of G-CSF treatment on cytokine secretions as that in NOMO-1 cells was observed in human monocytes.


CONCLUSIONS
Our data suggest that G-CSF directly affects monocytes and modulates their cytokine secretion. NOMO-1 cells can provide an alternate model for in vitro culture of monocytes to investigate the effects of G-CSF on cytokine secretion by these cells.
Saito
Masahiro
M
Department of Developmental Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
Kiyokawa
Nobutaka
N
Taguchi
Tomoko
T
Suzuki
Kyoko
K
Sekino
Takaomi
T
Mimori
Kenichi
K
Suzuki
Toyo
T
Nakajima
Hideki
H
Katagiri
Yohko U
YU
Fujimura
Junya
J
Fujita
Hiroo
H
Ishimoto
Koichi
K
Yamashiro
Yuichiro
Y
Fujimoto
Junichiro
J
D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor