TY - JOUR
T1 - Production of adrenomedullin in macrophage cell line and peritoneal macrophage
AU - Kubot, Atsushi
AU - Minamino, Naoto
AU - Isumi, Yoshitaka
AU - Katafuchi, Takeshi
AU - Kangawa, Kenji
AU - Dohi, Kazuhiro
AU - Matsuo, Hisayuki
PY - 1998/7/3
Y1 - 1998/7/3
N2 - We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-γ (IFN-γ) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7- fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-γ, whereas IFN-γ completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-β dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor α (TNF-α) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-α and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.
AB - We demonstrate that adrenomedullin (AM) is produced and secreted from cultured murine monocyte/macrophage cell line (RAW 264.7) as well as mouse peritoneal macrophage. Immunoreactive (IR) AM secreted from RAW 264.7 cells was chromatographically identified to be native AM. To elucidate the regulation mechanism of AM production in macrophage, we examined the effects of various substances inducing differentiation or activation of monocyte/macrophage. Phorbol ester (TPA), retinoic acid (RA), lipopolysaccharide (LPS), and interferon-γ (IFN-γ) increased AM production 1.5-7-fold in RAW 264.7 cells in a dose- as well as time-dependent manner. By LPS stimulation, the AM mRNA level in RAW 264.7 cells was augmented up to 7- fold after 14 h incubation. RA exerted a synergistic effect when administered with TPA, LPS, or IFN-γ, whereas IFN-γ completely suppressed AM production in RAW 264.7 cells stimulated with LPS. Dexamethasone, hydrocortisone, estradiol, and transforming growth factor-β dose-dependently suppressed AM production in RAW 264.7 cells. AM production was also investigated in mouse peritoneal macrophage. Primary mouse macrophage secreted IR-AM at a rate similar to that of RAW 264.7 cells, and its production was enhanced 9-fold by LPS stimulation. AM was found to increase basal secretion of tumor necrosis factor α (TNF-α) from RAW 264.7 cells, whereas AM suppressed the secretion of TNF-α and interleukin-6 from that stimulated with LPS. Thus, macrophage should be recognized as one of the major sources of AM circulating in the blood. Especially in cases of sepsis and inflammation, AM production in macrophage is augmented, and the secreted AM is deduced to function as a modulator of cytokine production.
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U2 - 10.1074/jbc.273.27.16730
DO - 10.1074/jbc.273.27.16730
M3 - Article
C2 - 9642228
AN - SCOPUS:0032479432
SN - 0021-9258
VL - 273
SP - 16730
EP - 16738
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 27
ER -