Cytokine-mediated regulation of granulocyte colony-stimulating factor production.
Granulocyte colony-stimulating factor (G-CSF) is an important regulator of granulopoiesis and an inducer of T helper 2 (Th2)-related cytokines. In this study we investigated the mechanism of cytokine-modulated G-CSF production in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) and bone marrow stromal cells (BMSC). In PBMC, LPS significantly induced G-CSF and interleukin (IL)-1, an inducer of G-CSF. Both were partly inhibited by IL-4, IL-6 and IL-10. None of these effects were the result of altered monocyte activation or proliferation. The effects of IL-4 and IL-10 appeared to be independent of IL-1 suppression or IL-1 receptor antagonist (IL-1ra) induction, but rather seemed to involve a blockade of IL-1 function, in addition to a blockade of IL-1-independent stimulatory effects on G-CSF production. The effect of the IL-6-induced suppression of G-CSF production differed from that of IL-4 and IL-10 in that it was much less pronounced and could be partially overridden by addition of functional IL-1, yet it also appeared to involve the interference with IL-1 function and the suppression of IL-1-independent mechanisms. In BMSC, G-CSF synthesis was regulated differently. Here, IL-1 was the main stimulator of G-CSF release, and the effect of IL-1 was neither affected by IL-10 nor IL-6, while IL-4 had a stimulatory effect. Thus, G-CSF production was found to be differently regulated in distinct cellular compartments, and a cross-regulation between these might be facilitated by IL-4-, IL-6- and IL-10-induced inhibition of IL-1. These results could be important for the understanding of G-CSF production in neutropenic patients during severe infection.
Hannen
M
M
Department of Pediatric Hematology and Oncology, Center of Child Health, Heinrich-Heine-University Düsseldorf Medical Center, Germany.
Banning
U
U
Bönig
H
H
Kim
Y M
YM
Shin
D I
DI
Lorenz
I
I
Seeger
K
K
Körholz
D
D
D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D015847:Interleukin-4