Granulocyte macrophage colony stimulating factor (GM-CSF) biological actions on human dermal fibroblasts

Fibroblasts are involved in all pathologies characterized by increased Extr aCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macr ophage-Colony Stimulating Factor (GM-CSF) is a cytokine isolated as an hemo poietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the recep tor for GM-CSF (GM-CSFR) on human normal skin fibroblasts from healthy subj ects (NFPC) and on a human normal fibroblast cell line (NHDF) and we try to investigate the biological effects of this cytokine. Human normal fibrobla sts were cultured with different doses of GM-CSF to study the effects of th is factor on GM-CSFR expression, on cell proliferation and adhesion structu res. In addition we studied the production of some Extra-Cellular Matrix (E CM) components such as Fibronectin, Tenascin and Collagen I. The growth rat e of fibroblasts from healthy donors (NFPC) is not augmented by GM-CSF stim ulation in spite of increased expression of the GM-CSFR. On the contrary, t he proliferation of normal human dermal fibroblasts (NHDF) cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis a ctivity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such "differentiation" is a n important event induced by such cytokine.