Interleukin-1 stimulation stabilizes GM-CSF mRNA in human vascular endothelial cells: preliminary studies on the role of the 3' AU rich motif.
To date, the notion that the AU rich motif in the 3' UT of GM-CSF mRNA can function as an IL-1 response element has not been adequately examined. We suspect that it must play some role because virtually all IL-1 inducible gene have AU rich 3' untranslated regions. Thus, we will continue to address these technical problems so that the hypothesis can be more clearly tested. Nonetheless, we can state with reasonable certainty that: 1) IL-1 induces expression of GM-CSF in EC by inducing accumulation of mRNA, 2) the GM-CSF gene is constitutively transcribed but the half life of the mRNA is short, 3) IL-1 induced mRNA accumulation results from stabilization of the transcript, 4) although most IL-1 responsive genes have AU-rich domains in their 3' untranslated regions, it is not yet clear that these AU-rich regions are sufficient to function as an IL-1 response element, and 5) murine L cells cannot be used for studies on the molecular biology of cytokine induction by IL-1.
Molecular Hematology Laboratory, V.A. Medical Center, Portland, OR.
G C
GC
Bagby
G
G
Shaw
M C
MC
Heinrich
S
S
Hefeneider
M A
MA
Brown
T G
TG
DeLoughery
G M
GM
Segal
L
L
Band
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006207:Half-Life; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor