TY - JOUR
T1 - Interleukin-4 enhances murine bone marrow macrophage M-CSF receptor expression by a posttranscriptional mechanism
AU - Gibbons, R.
AU - Ross, F. P.
AU - Perkins, S. L.
AU - Lacey, D. L.
AU - Martin, J.
AU - Ebner, R.
AU - Teitelbaum, S. L.
AU - Kahn, A. J.
PY - 1994
Y1 - 1994
N2 - Activated T-lymphocytes secrete interleukin-4 (IL-4), which has been shown to modulate a variety of monocyte activities requiring monocyte/macrophage colony-stimulating factor (M-CSF). To account for this interaction, we postulated that IL-4 acts on target cells by altering the expression of the M-CSF receptor (M-CSF(r)). To test this hypothesis, murine bone marrow macrophages were cultured under conditions that down-regulate M-CSF(r) and the effect of IL-4 on the reexpression of the receptor measured by binding of 125I-labeled M-CSF to the cells. The data show that incubation with IL-4 results in a dose-dependent, 2-3x increase in M-CSF(r) with no change in binding affinity and a maximal effect on binding at about 12 h. This increase in M-CSF(r) is dependent upon new, specific protein synthesis as shown by the inhibitory action of cycloheximide, and gel analysis of radiolabeled, specific protein, immunoprecipitated with anti-M-CSF(r) antibody. Treatment with IL-4 does not stimulate M-CSF(r) mRNA expression but, consistent with enhanced receptor levels, does result in a heightened proliferative response to M-CSF. Thus, IL-4 affects M-CSF treated monocytic cells, at least in part, by altering the expression of M-CSF(r).
AB - Activated T-lymphocytes secrete interleukin-4 (IL-4), which has been shown to modulate a variety of monocyte activities requiring monocyte/macrophage colony-stimulating factor (M-CSF). To account for this interaction, we postulated that IL-4 acts on target cells by altering the expression of the M-CSF receptor (M-CSF(r)). To test this hypothesis, murine bone marrow macrophages were cultured under conditions that down-regulate M-CSF(r) and the effect of IL-4 on the reexpression of the receptor measured by binding of 125I-labeled M-CSF to the cells. The data show that incubation with IL-4 results in a dose-dependent, 2-3x increase in M-CSF(r) with no change in binding affinity and a maximal effect on binding at about 12 h. This increase in M-CSF(r) is dependent upon new, specific protein synthesis as shown by the inhibitory action of cycloheximide, and gel analysis of radiolabeled, specific protein, immunoprecipitated with anti-M-CSF(r) antibody. Treatment with IL-4 does not stimulate M-CSF(r) mRNA expression but, consistent with enhanced receptor levels, does result in a heightened proliferative response to M-CSF. Thus, IL-4 affects M-CSF treated monocytic cells, at least in part, by altering the expression of M-CSF(r).
UR - http://www.scopus.com/inward/record.url?scp=0028197656&partnerID=8YFLogxK
M3 - Article
C2 - 8061119
AN - SCOPUS:0028197656
SN - 0277-6766
VL - 13
SP - 85
EP - 92
JO - Lymphokine and Cytokine Research
JF - Lymphokine and Cytokine Research
IS - 2
ER -