TY - JOUR
T1 - Differential Regulation of Metalloelastase Activity in Murine Peritoneal Macrophages by Granulocyte-Macrophage Colony-Stimulating Factor and Macrophage Colony-Stimulating Factor
AU - Kumar, Rakesh
AU - Dong, Zhongyun
AU - Fidler, Isaiah J.
PY - 1996/12/1
Y1 - 1996/12/1
N2 - We investigated the regulation of elastase activity in murine peritoneal macrophages by different cytokines and bacterial LPS. Thioglycolate-elicited mouse peritoneal exudate macrophages secrete a metalloproteinase that degrades elastin. Incubation of peritoneal exudate macrophages with LPS and IFN-γ significantly inhibited the production of elastase by a mechanism independent of nitric oxide, superoxide, and hydrogen peroxide. The cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, TGF-α and -β, basic fibroblast growth factor, monocyte chemotactic factor-1, and granulocyte CSF (G-CSF) had no significant effect on the production of elastase by macrophages. In contrast, granulocyte-macrophage CSF (GM-CSF) increased the production of elastase in a dose-dependent manner, and with macrophage CSF (M-CSF) inhibited it. Elastin zymography demonstrated that the modulation of elastolytic activity in macrophages was associated with changes in the level of metalloelastase protein. The stimulation of elastase activity by GM-CSF and the inhibition of elastase activity by LPS, IFN-γ, and M-CSF occurred at the level of transcription. LPS and M-CSF also augmented the expression level of tissue inhibitors of metalloproteinase mRNA. The increased mRNA steady state level of murine macrophage elastase induced by GM-CSF resulted from both increased transcription and enhanced stability. The modulation of metalloelastase activity in macrophages by IFN-γ, M-CSF, and GM-CSF suggests that these molecules may control the degradation of elastin fibers in lungs or blood vessels.
AB - We investigated the regulation of elastase activity in murine peritoneal macrophages by different cytokines and bacterial LPS. Thioglycolate-elicited mouse peritoneal exudate macrophages secrete a metalloproteinase that degrades elastin. Incubation of peritoneal exudate macrophages with LPS and IFN-γ significantly inhibited the production of elastase by a mechanism independent of nitric oxide, superoxide, and hydrogen peroxide. The cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, TGF-α and -β, basic fibroblast growth factor, monocyte chemotactic factor-1, and granulocyte CSF (G-CSF) had no significant effect on the production of elastase by macrophages. In contrast, granulocyte-macrophage CSF (GM-CSF) increased the production of elastase in a dose-dependent manner, and with macrophage CSF (M-CSF) inhibited it. Elastin zymography demonstrated that the modulation of elastolytic activity in macrophages was associated with changes in the level of metalloelastase protein. The stimulation of elastase activity by GM-CSF and the inhibition of elastase activity by LPS, IFN-γ, and M-CSF occurred at the level of transcription. LPS and M-CSF also augmented the expression level of tissue inhibitors of metalloproteinase mRNA. The increased mRNA steady state level of murine macrophage elastase induced by GM-CSF resulted from both increased transcription and enhanced stability. The modulation of metalloelastase activity in macrophages by IFN-γ, M-CSF, and GM-CSF suggests that these molecules may control the degradation of elastin fibers in lungs or blood vessels.
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M3 - Article
C2 - 8943420
AN - SCOPUS:0030469388
SN - 0022-1767
VL - 157
SP - 5104
EP - 5111
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -