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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
Author(s) -
Mantovani Luisa,
Henschler Reinhard,
Brach Marion A.,
Mertelsmann Roland H.,
Herrmann Friedhelm
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80213-m
Subject(s) - tumor necrosis factor alpha , biology , macrophage colony stimulating factor , interleukin , microbiology and biotechnology , protein kinase c , haematopoiesis , colony stimulating factor , cytokine , macrophage , cancer research , immunology , signal transduction , biochemistry , stem cell , in vitro
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.