IL-4 down-regulates IL-2-, IL-3-, and GM-CSF-induced cytokine gene expression in peripheral blood monocytes.
IL-4, a product of the T-helper 0 (Th0) and 2 (Th2) subset, was originally described as a B-cell stimulatory factor and has subsequently been found to suppress IL-1 alpha, IL-1 beta, IL-6, IL-8, and TNF-alpha gene expression in monocytes stimulated with LPS, and to upregulate IL-1 receptor antagonist (IL1-RA) gene expression. In this study we investigated the effect of IL-4 on the expression of cytokine genes in monocytes evoked by other T-helper cell cytokines: IL-2, IL-3, and GM-CSF. IL-4 down-regulated mRNA accumulation of the proinflammatory cytokines IL-1 beta, IL-8, and TNF-alpha in monocytes stimulated with IL-2, IL-3, and GM-CSF. IL-4 also suppressed the IL-2-induced IL-6 mRNA expression. Temporal analysis of the IL-4 down-regulatory effect on the IL-2-, IL-3-, or GM-CSF-induced proinflammatory cytokine gene expression in monocytes provided evidence that IL-4 acts predominantly on the post-transcriptional level. This was supported by the observation that the down-regulatory capacity of IL-4 appeared to be dependent on de novo protein synthesis. IL-4 did not exert significant influence on the induction of expression of IL-1-RA or various CSFs by IL-2, IL-3, and GM-CSF.(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
D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics*; D015536:Down-Regulation / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000502:physiology*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects
D016207:Cytokines; D007376:Interleukin-2; D007377:Interleukin-3; D014157:Transcription Factors; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide