IL-6 stimulates annexin 1 expression and translocation and suggests a new biological role as class II acute phase protein.
Annexin 1 (Ax 1), a protein whose synthesis and secretion are induced during the inflammatory response, has been proposed as a mediator of the anti-inflammatory action of glucocorticoids. To gain insight into a broader role of Ax 1 during the inflammatory response, the authors have investigated how pro-inflammatory cytokines [interleukin 1 (IL-1), IL-6 and tumour necrosis factor alpha (TNF-alpha)] affect Ax 1 expression and regulation at transcriptional and translational levels. The authors show that induction of the Ax 1 protein and its translocation to the cell membrane are stimulated by interleukin 6. However neither IL-1 nor TNF-alpha display these effects. Analysis of 5'-deletion mutants and the full length Ax 1 promoter fused to a luciferase reporter gene using transient transfections of human lung adenocarcinoma A 549 cells identified a unique 30 bp region of the Ax 1 promoter as critical for the responsiveness of the reporter gene to IL-6 and dexamethasone. Gel retardation and supershift assays showed that IL-6 stimulation is mediated by a C/EBP beta-like transcriptional factor. These data suggest that Ax 1 may participate in host defence as a new acute class II phase protein.
Institut Cochin de Génétique Moléculaire, INSERM U-332, Paris, France. Solito@icgm.cochin.inserm.fr
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D000209:Acute-Phase Proteins / Q000502:physiology*; D000230:Adenocarcinoma; D017305:Annexin A1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004586:Electrophoresis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D015735:Mifepristone / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D017305:Annexin A1; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D015735:Mifepristone; D003907:Dexamethasone