Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene.

摘要: One class of genes coding for the acute-phase proteins (acute-phase genes) is induced by interleukin 6 (IL-6) through human transcription factor NF-IL-6 and its rat homolog IL-6-DBP/LAP. A second class, represented alpha 2 macroglobulin gene, utilizes a different IL-6 response element (IL-6-RE) DNA-binding interacting with this element, so-called IL-6-RE binding (IL-6 RE-BPs). Human Hep3B HepG2 hepatoma, U266 myeloma, CESS lymphoblastoid cells contain RE-BPs that form complexes, IL-6-RE, gel mobilities indistinguishable from those corresponding complexes liver cells. The ability to these was in hepatoma maximum reached after 4 h required ongoing protein synthesis. Multiple copies an 18-bp containing core were sufficient confer both induction synergistic plus glucocorticoids minimal promoters. synergism blocked receptor antagonist RU486 thus dependent on glucocorticoid (GR). However, contained no consensus GR-binding site, recombinant GR did not bind at sequence. Therefore, probably achieved indirect effect glucocorticoid-activated intermediate gene RE-BPs. RE-BP had molecular weight 102 +/- 10 kDa distinct must activate two classes least nuclear proteins: NF-IL-6/IL-6-DBP/LAP RE-BP.