Contribution of interleukin-11 and prostaglandin(s) in lipopolysaccharide-induced bone resorption in vivo
Contribution of interleukin-11 and prostaglandin(s) in lipopolysaccharide-induced bone resorption in vivo
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DOI：
10.1128/iai.70.7.3915-3922.2002
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发表时间：
2002-07-01
影响因子：
3.1
通讯作者：
Amar, S
中科院分区：
文献类型：
--
作者：
Li, L;Khansari, A;Amar, S
我们以前证明，白细胞介素-1（IL-1）和肿瘤坏死因子（TNF）的活动，只有部分帐户的局部应用脂多糖（LPS）诱导的小鼠颅骨骨吸收。本研究旨在确定IL-11和前列腺素（PG [s]）在体内LPS诱导的骨吸收中的作用和相对贡献。将一次性剂量的LPS注射到覆盖缺乏I型IL-1受体的小鼠（1L-1RI（-/-））、缺乏TNF受体p55和IL-1RI的小鼠（TNFRp55（-/-）-IL-1RI（-/-））和野生型小鼠的颅盖的皮下组织中。然后用抗IL-11单克隆抗体（MAb）、吲哚美辛或磷酸盐缓冲盐水（PBS）注射处理小鼠，并在5天后处死。抗酒石酸酸性磷酸酶（TRAP）染色的组织切片进行定量的组织形态学分析。在低剂量的LPS（100 μ g/小鼠）下，发现破骨细胞覆盖的骨表面的百分比在三种品系的小鼠中相似。抗IL-11单克隆抗体使增加降低了37%，吲哚美辛降低了46%。在较高剂量的LPS（500 μ g/小鼠）下，我们发现野生型小鼠的这些百分比增加了8倍，在用相同品系小鼠的生理盐水-PBS对照组的值进行标准化后，IL-1RI（-/-）和TN-FRp55（-/-）-IL-1RI（-/-）小鼠的这些百分比增加了5倍。在野生型小鼠中，这种增加分别减少了55%和69%，在用抗IL-11 MAb或吲哚美辛处理的IL-1RI（-/-）和TNFRp55（-/-）-IL-1RI（-/-）小鼠中分别减少了50%和57%。我们的研究结果表明，在体内，在低剂量的LPS（100 μ g/小鼠），LPS诱导的骨吸收是由IL-11和PG介导的，而在高剂量的LPS（500 μ g/小鼠），它是由IL-11，PG，IL-1，和TNF信号介导的，IL-11和PG介导的LPS诱导的骨吸收，通过增强破骨细胞生成独立的IL-1或TNF信号。
We previously demonstrated that interleukin-1 (IL-1) and tumor necrosis factor (TNF) activities only partially account for calvarial bone resorption induced by local application of lipopolysaccharide (LPS) in mice. The present study was undertaken to determine the role and relative contribution of IL-11 and prostaglandin(s) (PG[s]) in LPS-induced bone resorption in vivo. A one-time dose of LPS was injected into the subcutaneous tissue overlying calvaria of mice lacking IL-1 receptor type I (1L-1RI(-/-)), mice lacking TNF receptor p55 and IL-1RI (TNFRp55(-/-)-IL-1RI(-/-)), and wild-type mice. Mice were then treated with injections of anti-IL-11 monoclonal antibody (MAb), indomethacin, or phosphate-buffered saline (PBS) and sacrificed 5 days later. Histological sections stained for tartrate-resistant acid phosphatase (TRAP) were quantified by histomorphometric analysis. At low doses of LPS (100 mug/mouse), the percentages of bone surface covered by osteoclasts were found to be similar in three strains of mice. The increase was reduced by 37% with anti-IL-11 MAb and by 46% with indomethacin. At higher doses of LPS (500 mug/mouse), we found an eightfold increase in these percentages in wild-type mice and a fivefold increase in these percentages in IL-1RI(-/-) and TN-FRp55(-/-)-IL-1RI(-/-) mice after normalizing with the value from the saline-PBS control group in the same strain of mice. The increase was reduced by 55 and 69% in wild-type mice and by 50 and 57% in IL-1RI(-/-) and TNFRp55(-/-)-IL-1RI(-/-) mice treated with anti-IL-11 MAb or indomethacin, respectively. Our findings suggest that in vivo, at low doses of LPS (100 mug/mouse), LPS-induced bone resorption is mediated by IL-11 and PGs, while at high doses of LPS (500 mug/mouse), it is mediated by IL-11, PGs, IL-1, and TNF signaling, IL-11 and PGs mediate LPS-induced bone resorption by enhancing osteoclastogenesis independently of the IL-1 or TNF signaling.