Human fibroblasts produce granulocyte-CSF, macrophage-CSF, and granulocyte-macrophage-CSF following stimulation by interleukin-1 and poly(rI).poly(rC)

Abstract

Electrophoretically pure human interleukin-1 (IL-1) beta was found to stimulate human fibroblasts in a monolayer culture to elaborate colony- stimulating activity (CSA). Supernatant fluids from cultures induced with increasing concentrations of IL-1 were found to stimulate colony formation of myeloid (CFU-GM), erythroid (BFU-E), and multipotent (CFU- GEMM) progenitor cells in a dose-dependent fashion. The effect on mixed colony formation, however, was less than on CFU-GM and BFU-E growth. Similar to IL-1, the synthetical double-stranded RNA poly(rI).poly(rC) also stimulated release of CSA by fibroblasts. The kinetics of IL-1- and poly(rI).poly(rC)-induced CSA release were found to be different, in that poly(rI).poly(rC)-induced CSA production occurred more slowly. Anti-IL-1 antiserum was able to completely neutralize the IL-1-induced CSA release, but had no effect on poly(rI).poly(rC)-induced CSF production, suggesting that the latter effect was mediated by other mechanisms than IL-1 in supernatant. By the use of specific immunologic assays, G-CSF, M-CSF, and GM-CSF could be identified in media conditioned by fibroblasts treated with IL-1 or poly(rI).poly(rC). Poly(rI).poly(rC) appeared to be a better inducer for M-CSF than IL-1.

Altered Response of Intestinal Mucosal Fibroblasts to Profibrogenic Cytokines in Inflammatory Bowel Disease

“…The effects that these mediators have on the fibroblast are potentially important in promoting the excessive collagen deposition observed in IBD. The fibroblast‐secreted growth factor macrophage‐colony stimulating factor (M‐CSF), which regulates macrophage proliferation (23,24), is also expressed at increased levels in the inflamed IBD intestinal wall (25). The effects that these soluble mediators have on the isolated fibroblast was, therefore, investigated to advance our understanding the fibrotic process and the role of the fibroblast in the IBD intestine.…”

GM-CSF, IL-1α, IL-β, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1α and TNF-α

“…Skin, synovial and pulmonary fibroblasts produce granulocyte-macrophage colony-stimulating faetor (GM-CSF). granulocyte colony-stimulating factor (G-CSF), leukaemia inhibitory factor (LiF), IL-1, IL-6 and IL-8 when stimulated with IL-1 or tumour necrosis factor (TNF) [1][2][3][4][5]. Adhesion molecules such as intercellular adhesion molecule-I (ICAM-I) and vascular cell adhesion moiecule-1 (VCAM-1) are expressed on the surface of fibroblasts [6,7], Cytokine secretion is increased by bacterial lipopolysaccharide (LPS) and viruses [8,9], suggesting a role in host defence.…”

The Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF): Basic Science and Clinical Application

“…In combina- Fig. 1 Cytoklne regulation 01 hematopoiesis tion with Interleukin-3 and erythropoetin GM-CSF stimulates megakaryocytopoietic as weil as erythropoietic progenitors (11,28,36,79,83). In addition to normal hematopoietic cells, GM-CSF stimulates proliferation of endothelial cells and keratinocytes (1,23,75).…”

“…In granulocytes, GM-CSF induces the secretion of interleukin-I, granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF). GM-CSF also stimulates histamin-release from mast cells (I, 28,30,75,90). GM-CSF also exerts its influence on the function of mature macrophages.…”

“…GM-CSF production has been demonstrated in T-Iymphocytes, natural killer cells, marrow stroma, activated macrophages, fibroblasts, endothelial cells, astrocytes and keratinocytes (6,16,28,35,35,43,51,57,89). T-Lymphocytes are probably the major source of GM-CSF.…”