Regulatory effects of T cell lymphokines on cytokine gene expression in monocytes.
Hematopoiesis is regulated by colony-stimulating factors (CSF) and many other cytokines. T helper cell and monocyte/macrophage interactions that take place in the immune response, resulting in the production of many cytokines, probably can influence inducible hematopoiesis. We investigated the effect of the T helper cell-derived lymphokines IL-2, IL-3, GM-CSF, and IFN-gamma, on the expression of cytokine genes in monocytes and compared this to LPS-induced cytokine gene expression in monocytes. To avoid inadvertent activation of monocytes, cells were purified by elutriation and cultured under serum-free, LPS-free, and nonadherent conditions. Similar to LPS, IL-2, IL-3, and GM-CSF induced the expression of IL-1 beta, IL-6, IL-8, TNF-alpha, and IL-1-RA genes in monocytes, but with some differences in the amount and kinetics of cytokine mRNA accumulation. Unlike LPS, IL-2, IL-3, and GM-CSF did not induce G-CSF and GM-CSF gene expression in monocytes. GM-CSF and IL-3 were the only inducers capable of expressing the M-CSF gene in monocytes. IL-2, IL-3, and GM-CSF showed no effect on the IL-10 gene while IFN-gamma appeared to have no effect on any of the cytokine genes studied in monocytes. These data indicate that in the immune response expression of the proinflammatory cytokine genes, IL-1 beta, IL-6, IL-8, and TNF-alpha, can occur and that autoregulatory control mechanisms, like the expression of IL-1-RA gene, are also activated.(ABSTRACT TRUNCATED AT 250 WORDS)
Cluitmans
F H
FH
Department of Hematology, University Medical Center, Leiden, The Netherlands.
Esendam
B H
BH
Landegent
J E
JE
Willemze
R
R
Falkenburg
J H
JH
D015152:Blotting, Northern; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008222:Lymphokines / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D016207:Cytokines; D007376:Interleukin-2; D007377:Interleukin-3; D008222:Lymphokines; D012333:RNA, Messenger; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor