TY - JOUR
T1 - CSF-1 (M-CSF) enhances the inflammatory response of fibronectin-primed macrophages
T2 - Pathways involved in activation of the cytokine network
AU - Kremlev, Sergey G.
AU - Chapoval, Andrei I.
AU - Evans, Robert
PY - 1998
Y1 - 1998
N2 - We have previously reported that the priming of thioglycollate-elicited peritoneal macrophages (PMφ), as a representative population of mono-nuclear phagocytes (MNP), by macrophage-colony-stimulating factor (M-CSF or CSF- 1) rendered these cells more susceptible to secondary stimulation by extracellular matrix (ECM) proteins, in particular fibronectin (FN), and that at least two β1 integrins, VLA 4 (α4β1 or CD49d) and VLA 5 (α5β1 or CD49e), regulate IL-6 gene expression when PMφ come into contact with FN. In this report, we focused our attention on resident PMφ, as a more mature/differentiated MNP subpopulation. By using granulocyte-macrophage colony-stimulating factor (GM-CSF)- and IL-6-knockout (null) mice, we demonstrated that the cooperative effect between CSF-1 and FN in IL-6 release was a result of a sequential stimulation of the GM-CSF, but not the TNF-α, gene via interaction with VLA 5. We also showed that regardless of the presence or absence of CSF-1 or FN, IL-6 inhibits GM-CSF and TNF-α gene expression in an autocrine manner. The observed effects were specific because CSF-1 enhanced VLA 5 expression and blocking FN-treated resident PMφ in vitro with VLA 5 monoclonal antibodies inhibited the IL-6 response. We found that treatment of resident PMφ with the protein kinase C inhibitor, staurosporine, and the activator, phorbol myristate acetate (PMA), resulted in marked modulation of either FN- or FN/CSF-1-induced cytokine release. An increased level of VLA 5 expression was observed in PMA-treated resident PMφ. We concluded that in inflammatory processes, CSF-1 drives a number of pathways involved in the regulation of the expression of several genes and renders MNP highly susceptible to stimulation by ECM proteins that transform the MNP into secretory inflammatory cells.
AB - We have previously reported that the priming of thioglycollate-elicited peritoneal macrophages (PMφ), as a representative population of mono-nuclear phagocytes (MNP), by macrophage-colony-stimulating factor (M-CSF or CSF- 1) rendered these cells more susceptible to secondary stimulation by extracellular matrix (ECM) proteins, in particular fibronectin (FN), and that at least two β1 integrins, VLA 4 (α4β1 or CD49d) and VLA 5 (α5β1 or CD49e), regulate IL-6 gene expression when PMφ come into contact with FN. In this report, we focused our attention on resident PMφ, as a more mature/differentiated MNP subpopulation. By using granulocyte-macrophage colony-stimulating factor (GM-CSF)- and IL-6-knockout (null) mice, we demonstrated that the cooperative effect between CSF-1 and FN in IL-6 release was a result of a sequential stimulation of the GM-CSF, but not the TNF-α, gene via interaction with VLA 5. We also showed that regardless of the presence or absence of CSF-1 or FN, IL-6 inhibits GM-CSF and TNF-α gene expression in an autocrine manner. The observed effects were specific because CSF-1 enhanced VLA 5 expression and blocking FN-treated resident PMφ in vitro with VLA 5 monoclonal antibodies inhibited the IL-6 response. We found that treatment of resident PMφ with the protein kinase C inhibitor, staurosporine, and the activator, phorbol myristate acetate (PMA), resulted in marked modulation of either FN- or FN/CSF-1-induced cytokine release. An increased level of VLA 5 expression was observed in PMA-treated resident PMφ. We concluded that in inflammatory processes, CSF-1 drives a number of pathways involved in the regulation of the expression of several genes and renders MNP highly susceptible to stimulation by ECM proteins that transform the MNP into secretory inflammatory cells.
KW - Cytokines
KW - Extracellular matrix
KW - Inflammation
KW - Monocytes/macrophages
KW - Transgenic/knockout
UR - http://www.scopus.com/inward/record.url?scp=0032229916&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032229916&partnerID=8YFLogxK
U2 - 10.1159/000069449
DO - 10.1159/000069449
M3 - Article
C2 - 11061591
AN - SCOPUS:0032229916
SN - 1018-8916
VL - 16
SP - 228
EP - 243
JO - Natural Immunity
JF - Natural Immunity
IS - 5-6
ER -