IL-6 stimulates annexin 1 expression and translocation and suggests a new biological role as class II acute phase protein

Annexin 1 (As 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-l), IL-6 and tumour necrosis factor alpha. (TNF-alpha)] affect As 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-l 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 nem; acute class II phase protein, (C) 1998 Academic Press.