Prostaglandin regulation of macrophage collagenase production.
Prostaglandin regulation of macrophage collagenase production.
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前列腺素调节巨噬细胞胶原酶的产生。
DOI：
10.1073/pnas.74.11.4955
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发表时间：
1977
影响因子：
11.1
通讯作者：
S. E. Mergenhagen
中科院分区：
文献类型：
--
作者：
L. Wahl;C. Olsen;A. Sandberg;S. E. Mergenhagen
吲哚美辛显著抑制内毒素刺激的巨噬细胞产生胶原酶（EC 3.4.24.3），表明洋地黄素（PGs）介导该作用。通过加入10 nM的外源性PGE 2克服了吲哚美辛对胶原酶产生的抑制作用，而加入0.1和1.0 μ m的PGE 2使酶产生增加到内毒素所达到的3倍。尽管向巨噬细胞培养物中单独添加前列腺素并不能刺激胶原酶的产生，但同时添加PGE 1或PGE 2和内毒素可使胶原酶活性增强2至10倍。这种增加在10 nM的PGE浓度下是可检测的，并且在0.1-1.0微米下是最佳的。PGF 2 α对内毒素刺激的巨噬细胞产生胶原酶的增强或吲哚美辛抑制的培养物中胶原酶的恢复几乎没有影响。放射免疫分析显示，巨噬细胞暴露于内毒素分泌的前列腺素E2比未受刺激的细胞多40倍。暴露于内毒素后4小时检测到PGE 2的增加，并在14小时达到最大值。培养基中PGE 2的峰值浓度与恢复吲哚美辛处理的培养物中胶原酶生产所需的外源性PGE 2（约10 nM）相似。这些发现表明PGE参与巨噬细胞的内毒素活化，从而产生胶原酶。
The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibitions of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0 micrometer PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2- to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 micrometer. PGF2alpha had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase.