Premium
Interleukin‐6‐induced plasminogen gene expression in murine hepatocytes is mediated by transcription factor CCAAT/enhancer binding protein β (C/EBPβ)
Author(s) -
Bannach F. G.,
GutierrezFernandez A.,
Parmer R. J.,
Miles L. A.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.01022.x
Subject(s) - microbiology and biotechnology , enhancer , ccaat enhancer binding proteins , transcription factor , electrophoretic mobility shift assay , biology , gene expression , promoter , transcription (linguistics) , downregulation and upregulation , mapk/erk pathway , gene , signal transduction , nuclear protein , biochemistry , linguistics , philosophy
Summary. An emerging area of research has demonstrated that plasminogen functions in the acute‐phase response to tissue injury, neoplastic growth or infection. We have previously shown that the acute‐phase mediator, interleukin (IL)‐6, increases circulating plasminogen levels via upregulation of plasminogen promoter activity. We also identified a putative IL‐6 responsive element (nt −791 to −783; IL6‐RE) in the plasminogen gene that is required for maximal stimulation of promoter activity by IL‐6. For the present study, we investigated the transcription factors and signaling pathway mediating the response of the plasminogen gene to IL‐6. In electrophoretic mobility shift assays (EMSAs), a radiolabeled oligonucleotide IL6‐RE probe formed specific complexes with nuclear proteins from untreated hepatocytic cells. The extent of complex formation was markedly increased using nuclear proteins from IL‐6‐treated cells. Complex formation was abolished by an oligonucleotide with the consensus CCAAT/enhancer binding protein (C/EBP) sequence. Furthermore, complexes were supershifted by antibodies to C/EBPβ. Treatment of Hepa 1‐6 cells with the mitogen‐activated protein kinase (MAPK) inhibitor, PD‐98059, inhibited IL‐6‐stimulated plasminogen promoter activity. These results suggest that transcription factor C/EBPβ and the MAPK pathway play key roles in the response of the plasminogen gene to IL‐6, thus elucidating a major mechanism by which the plasminogen system is upregulated to perform its crucial functions in the acute‐phase response.