IL-6 STIMULATES ANNEXIN-1 EXPRESSION AND TRANSLOCATION AND SUGGESTS ANEW 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 t he anti-inflammatory action of glucocorticoids. To gain insight into a broader role of Ax 1 during the inflammatory response, the authors ha ve investigated how pro-inflammatory cytokines [interleukin 1 (IL-l), IL-6 and tumour necrosis factor alpha. (TNF-alpha)] affect As 1 expres sion and regulation at transcriptional and translational levels. The a uthors show that induction of the Ax 1 protein and its translocation t o the cell membrane are stimulated by interleukin 6, However neither I L-l nor TNF-alpha display these effects, Analysis of 5'-deletion mutan ts and the full length Ax 1 promoter fused to a luciferase reporter ge ne using transient transfections of human lung adenocarcinoma A 549 ce lls 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 sugg est that Ax 1 may participate in host defence as a nem; acute class II phase protein, (C) 1998 Academic Press.