Constitutive and Interleukin-1 (IL-1)-Inducible Factors Interact with the IL-1-Responsive Element in the IL-6 Gene

Hiroshi Isshiki, Shizuo Akira, Osamu Tanabe, Toshihiro Nakajima, Takuya Shimamoto, Toshio Hirano, Tadamitsu Kishimoto

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242 Citations (Scopus)


The interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans-acting factors responsible for IL-1-induced IL-6 gene expression. Studies on the 5′ deletion mutants of the human IL-6 gene suggested that the IL-1-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14-bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-1-responsive element in the IL-6 gene.

Original languageEnglish
Pages (from-to)2757-2764
Number of pages8
JournalMolecular and cellular biology
Issue number6
Publication statusPublished - 1990 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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