THE TYPE-II HEMOPEXIN INTERLEUKIN-6 RESPONSE ELEMENT PREDOMINATES THETRANSCRIPTIONAL REGULATION OF THE HEMOPEXIN ACUTE-PHASE RESPONSIVENESS

Hemopexin (Hx) is induced during the acute phase response (APR) by the cytokine interleukin (IL)-6. A type II IL-6 response element (RE) of the Hx gene has been characterized recently (J. Biol. Chem. (1994); 26 9, 12654-12661). To assess Hx gene regulation by other agents, various cytokines and growth factors were tested for their ability to induce Hx in rat hepatoma H-35 cells. IL-6-type cytokines, IL-1 beta and TNF- alpha, in contrast to transforming growth factor-beta (TGF-beta), hepa tocyte growth factor and insulin significantly increased Hx gene expre ssion. Chloramphenicol acetyltransferase (CAT) activity in H-35 cells transfected with constructs that contained the 5'-flanking Hx promoter region or multiple copies of the Hx IL-6-RE fused to the CAT gene was upregulated only by IL-6-type cytokines, although to varying degrees. These data indicate that signal transduction pathways mediated by IL- 6-type cytokines but not those by IL-1 beta and TNF-alpha converge on the common Hx IL-B-RE. (C) 1995 Academic Press. Inc.