Transforming growth factor beta 1 regulation of macrophage activation depends on the triggering stimulus.
We have examined the effects of transforming growth factor beta 1 (TGF-beta 1) on the regulation of murine bone marrow-derived macrophage function. TGF-beta, added simultaneously with or up to 4 h before interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS), inhibited macrophage leishmanicidal activity, nitrite (NO2-) production, and secretion of prostaglandin E2. In contrast, no effect of TGF-beta could be demonstrated on macrophages stimulated with IFN-gamma plus tumor necrosis factor-alpha (TNF-alpha) under the same conditions. These results suggested that TGF-beta inhibited LPS-induced triggering of macrophage activation, which was confirmed by studies with IFN-gamma-primed cells. Interestingly, when macrophages were pretreated with TGF-beta for 24 h, NO2- production in response to IFN-gamma plus TNF-alpha was also inhibited. Although control and IFN-gamma/LPS-stimulated macrophages were found to secrete latent TGF-beta, only the IFN-gamma/LPS cultures produced biologically active TGF-beta. Significantly, active TGF-beta was present at concentrations shown earlier to inhibit macrophage function.
Corradin
S B
SB
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Buchmuller-Rouiller
Y
Y
Smith
J
J
Suardet
L
L
Mauël
J
J
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D018313:Leishmania enriettii / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D009573:Nitrites / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D008070:Lipopolysaccharides; D009573:Nitrites; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone