Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA.
Transcription of the interleukin 1 beta (IL-1 beta) gene was studied by mRNA hybridization with a cDNA probe in the human promonocytic cell line U-937. Phorbol ester and lipopolysaccharide increased the steady-state level of IL-1 beta mRNA. Glucocorticoids markedly decreased IL-1 beta mRNA levels by two mechanisms. Transcription of the IL-1 gene was inhibited, as shown by in vitro transcription assays with nuclei isolated from glucocorticoid-treated cells. Moreover, kinetic analyses and pulse-labeling of mRNAs showed that glucocorticoids selectively decrease the stability of IL-1 beta mRNA, without affecting the stability of beta-actin and FOS mRNAs. Inhibition of the formation and effects IL-1 is a mechanism by which glucocorticoids can exert antiinflammatory and immunosuppressive effects.
Lee
S W
SW
Department of Immunology, Syntex Research, Palo Alto, CA 94303.
Tsou
A P
AP
Chan
H
H
Thomas
J
J
Petrie
K
K
Eugui
E M
EM
Allison
A C
AC
D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D004247:DNA; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone