IL-1 alpha induces granulocyte-macrophage colony-stimulating factor gene expression in murine B lymphocyte cell lines via mRNA stabilization.
IL-1 has been shown to induce granulocyte-macrophage (GM)-CSF production in several cell types including T lymphocytes, fibroblasts, and endothelial cells. We have previously demonstrated that bacterial LPS activates expression of the GM-CSF gene in murine B lymphocytes. Inasmuch as LPS is also an inducer of IL-1, we asked whether IL-1 could itself induce GM-CSF gene expression in B lymphocytes. The GM-CSF-dependent PT-18 cell line was used to detect GM-CSF biologic activity and a semi-quantitative polymerase chain reaction assay was developed to detect and measure GM-CSF mRNA. IL-1 alpha stimulated GM-CSF production by the murine B cell lines M12.4.1 and TH2.2 but not by the M12 line in a dose- and time-dependent fashion. GM-CSF mRNA expression in IL-1 alpha-treated M12.4.1 cells also increased in a dose- and time-dependent fashion. Nuclear run-on transcription assays revealed constitutive transcription of the GM-CSF gene in untreated M12.4.1 cells that did not change after IL-1 alpha treatment. Actinomycin D chase experiments indicated that IL-1 alpha increased GM-CSF mRNA stability in the M12.4.1 cells. These findings indicate that IL-1 alpha induces GM-CSF gene expression in murine B cell lines and that this event is posttranscriptionally controlled mainly at the level of mRNA stabilization.
Akahane
K
K
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892.
Cohen
R B
RB
Bickel
M
M
Pluznik
D H
DH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D015870:Gene Expression / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006207:Half-Life; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D003470:Culture Media; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor