Soluble human interleukin‐6‐receptor modulates interleukin‐6‐dependent N‐glycosylation of α1‐protease inhibitor secreted by HepG2 cells

FEBS Letters

Mackiewicz, Andrzej²  Schooltink, Heidi¹  Górny, Aleksander²  Laciak, Maria²  Heinrich, Peter C.¹  Rose-John, Stefan¹ 

[1] Institut für Biochemie der RWTH Aachen, Pauwelsstr. 30, D-5100 Aachen, Germany;Department of Cancer Immunology, Chair of Oncology, Academy of Medicine at Great Poland Cancer, Garbary 15, 62866 Poznan, Poland

关键词: Acute-phase response;    α1-Protease inhibitor;    Hepatoma cell;    Interleukin-6;    N-Glycosylation;    Soluble interleukin-6-receptor;    APP;    acute-phase proteins;    Con A;    concanavalin A;    CAIE;    crossed affinity-immunoelectrophoresis;    GlcNAc;    N-acetyl-glucosamine;    GnT;    GlcNAc-transferase;    IL-6;    interleukin-6;    IFN;    interferon;    LIF;    leukemia inhibitory factor;    PI;    a1-protease inhibitor;    rh;    recombinant human;    shIL-6-R;    soluble human interleukin-6-receptor;    TGF;    transforming growth factor;    TNF;    tumor necrosis factor;   

DOI  :  10.1016/0014-5793(92)81012-B

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interleukin-6 (IL-6) induces changes in gene expression and the N-glycosylation pattern of acute-phase proteins in hepatocytes. IL-6 exerts its action via a cell surface receptor complex consisting of an 80 kDa IL-6 binding protein (gp80) and a 130 kDa glycoprotein (gp130) involved in signal transduction. A genetically engineered gp80-derived soluble human IL-6-receptor (shIL-6-R) significantly enhanced the IL-6 effect on N-glycosylation changes (revealed by reactivity with the lectin—concanavalin A) of a₁-protease inhibitor (PI) secreted by human hepatoma cells (HepG2). Stable transfection of IL-6-cDNA into HepG2 cells (HepG2-IL-6) resulting in constitutive secretion of 2 μg of IL-6 per 10⁶ cells in 24 h led to a down-regulation of surface-bound gp80 and subsequent homologous desensitization or HepG2-IL-6 cells towards IL-6. Soluble human IL-6-R functionally substituted membrane-bound gp80 resulting in a reconstitution of responsiveness of HepG2-IL-6 cells.

【 授权许可】

Unknown