Cytokine regulation of interleukin-6 gene expression in astrocytes involves activation of an NF-kappa B-like nuclear protein.
The cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) induce interleukin-6 (IL-6) gene expression in astrocytes. The molecular mechanism(s) by which these cytokines activate IL-6 expression was examined by transient transfection of the human IL-6 promoter linked to the reporter gene CAT (IL-6-CAT) in primary rat astrocytes. We show that both IL-1 beta and TNF-alpha exert their effects through the IL-6 promoter to increase CAT activity, indicating that the cytokines act at the transcriptional level. Use of deletion mutants revealed that the NF-kappa B-like binding site is required for cytokine induction of IL-6 promoter activity. The correlary effects of IL-1 beta and TNF-alpha on DNA-binding proteins specific for this element were examined. Treatment of astrocytes with either cytokine leads to a rapid activation (15 min) of a nuclear protein which specifically complexes with the NF-kappa B-like binding region in the IL-6 promoter. These results suggest that TNF-alpha and IL-1 beta activate IL-6 gene expression in astrocytes by a mechanism(s) involving activation of an NF-kappa B-like protein.
Sparacio
S M
SM
Department of Cell Biology, University of Alabama, Birmingham 35294.
Zhang
Y
Y
Vilcek
J
J
Benveniste
E N
EN
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha