Regulation of rat liver acute phase genes by interleukin-6 and production of hepatocyte stimulating factors by rat hepatoma cells

G. H. Fey, Masahira Hattori, W. Northemann, L. J. Abraham, M. Baumann, T. A. Braciak, R. G. Fletcher, J. Gauldie, F. Lee, M. F. Reymond

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Abstract

A cis-acting DNA control element mediating the transcriptional regulation of IL6 (IL6-RE) was mapped in the promoter proximal 5'-flanking region of the rat α2M gene. Sequences closely resembling the core of this element, CTGGGA, are also present in the control regions of other IL6-regulated acute phase genes, including the rat α1AGP, T1- and T2-kininogen genes, the rat gamma-fibrinogen genes, and the human CRP and haptoglobin genes. IL6 and the protein kinase A activator forskolin were found to be able to negatively regulate the rat α1I3 gene in hepatoma cells. Two IL6 mRNA species of 1.2 and 2.4 kb, respectively, were observed in LPS-stimulated rat macrophage and IL1-stimulated rat fibroblast RNA preparations. The 1.2 kb species was approximately five times more abundant than the 2.4-kb species. In addition, a cDNA clone representing the 1.2 kb mRNA species was isolated and sequenced, and the amino acid sequence of the rat IL6 was deduced. A β-galactosidase IL6 fusion protein was expressed at high efficiency in E. coli and was used for immunization purposes. An IL6-like activity (IL6-LA), sharing HSF function with IL6/BSF-2, was produced by some, but not all rat hepatoma cell lines. Preliminary data suggest that the activity secreted by Fto2B cells could be structurally distinct from authentic IL6/BSF-2, although structural identity with IL6 has not been formally excluded. At least two rat hepatoma cell lines, HTC and H5, produce IL6 mRNA species of normal, characteristic size and, therefore, the IL6-like activities produced by these lines are probably identical with IL6.

Original languageEnglish
Pages (from-to)317-331
Number of pages15
JournalAnnals of the New York Academy of Sciences
Volume557
Publication statusPublished - 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fey, G. H., Hattori, M., Northemann, W., Abraham, L. J., Baumann, M., Braciak, T. A., Fletcher, R. G., Gauldie, J., Lee, F., & Reymond, M. F. (1989). Regulation of rat liver acute phase genes by interleukin-6 and production of hepatocyte stimulating factors by rat hepatoma cells. Annals of the New York Academy of Sciences, 557, 317-331.