Regulation of gene expression of macrophage‐colony stimulating factor in human fibroblasts by the acute phase response mediators interleukin (IL)‐1β, tumor necrosis factor‐α and IL‐6

FEBS Letters

Mantovani, Luisa¹  Herrmann, Friedhelm¹  Henschler, Reinhard¹  Brach, Marion A.¹  Mertelsmann, Roland H.¹ 

[1] Laboratory of Molecular Hematopoiesis, Department of Internal Medicine I, University of Freiburg, Freiburg, Germany

关键词: Macrophage-colony stimulating factor;    Gene expression;    Regulation;    Protein kinase C;    ANAE;    α-naphtylacetate-esterase;    CHX;    cyclohexemide;    CM;    conditioned medium;    CSFs;    colony stimulating factors;    FCS;    fetal serum calf;    H7;    1-(isoquinolinylsulfonyl)-2 methylpiperazine;    IL;    interleukin;    M-CSF;    macrophage-colony stimulating factor;    PAGE;    polyacrylamide gel electrophoresis;    PKC;    protein kinase C;    RP-HPLC;    reversed-phase high-performance liquid chromatography;    SDS;    sodium dodecyl sulfate;    SSC;    standard sodium citrate (1 × SSC = 0.15 M NaCl;    0.015 M sodium tricitrate;    pH 7.0);    TNF;    tumor necrosis factor;    TPA;    12-O-tetradecanoylphorbol-13-acetate;   

DOI  :  10.1016/0014-5793(91)80213-M

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Fibroblasts constitute a major element of the bone marrow stroma. They play a pivotal role in blood cell development by providing the scaffolding required for cellular organization and tissue cohesion and by producing soluble molecules including colony stimulating factors (CSFs) and various interleukins regulating hematopoiesis. Our data demonstrate that the acute phase response mediators interleukin (IL)-1 β, tumor necrosis factor (TNF)-α and IL-6 which are abundantly produced by activated monocytes, enhance levels of macrophage-colony stimulating factor (M-CSF) in fibroblasts by both transcriptional and post-transcriptional mechanisms. The action of these proteins to induce M-CSF transcript levels was dependent on synthesis of new proteins and was not mediated by protein kinase C (PKC) stimulation as depletion of cellular PKC pools by prolonged exposure of fibroblasts to phorbolester TPA did not prevent factor induced synthesis of M-CSF transcripts. However, blockade of PKC by the isoquinoline sulfonamide derivative H7 and thus inhibition of phosphorylation was associated with augmentation of the fibroblasts response to TNF-α and IL-6.

【 授权许可】

Unknown