Lipopolysaccharide promotes the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to lipopolysaccharide is different from that of macrophages
Lipopolysaccharide promotes the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to lipopolysaccharide is different from that of macrophages
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DOI：
10.4049/jimmunol.170.7.3688
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Takahashi, N
中科院分区：
文献类型：
--
作者：
Itoh, K;Udagawa, N;Takahashi, N
脂多糖是导致炎性骨丢失的病原体。单核细胞和巨噬细胞响应于LPS产生促炎细胞因子如IL-1、TNF-α和IL-6。我们研究了LPS对体外形成的破骨细胞功能的影响，并与其对骨髓巨噬细胞（破骨细胞前体）的影响进行了比较。破骨细胞和骨髓巨噬细胞表达Toll样受体4（TLR 4）和CD 14的mRNA，LPS受体系统的组成部分。LPS诱导破骨细胞I-κ B快速降解，刺激破骨细胞存活。LPS不能支持来自C3 H/HeJ小鼠的破骨细胞的存活，其在TLR 4基因中具有错义突变。LPS促进的破骨细胞存活不受任何已知可延长破骨细胞存活的细胞因子介导，如IL-1 β、TNF-α和NF-κ B配体的受体激活剂。LPS刺激骨髓巨噬细胞和腹腔巨噬细胞产生促炎细胞因子，如IL-1 β、TNF-α和IL-6，但在破骨细胞中不产生。这些结果表明，破骨细胞响应LPS通过TLR 4，但破骨细胞的特性是完全不同的，从它们的前体，巨噬细胞，在响应LPS的促炎细胞因子的生产。
Lipopolysaccharide is a pathogen that causes inflammatory bone loss. Monocytes and macrophages produce proinflammatory cytokines such as IL-1, TNF-alpha, and IL-6 in response to LPS. We examined the effects of LPS on the function of osteoclasts formed in vitro in comparison with its effect on bone marrow macrophages, osteoclast precursors. Both osteoclasts and bone marrow macrophages expressed mRNA of Toll-like receptor 4 (TLR4) and CD14, components of the LPS receptor system. LPS induced rapid degradation of I-kappaB in osteoclasts, and stimulated the survival of osteoclasts. LPS failed to support the survival of osteoclasts derived from C3H/HeJ mice, which possess a missense mutation in the TLR4 gene. The LPS-promoted survival of osteoclasts was not mediated by any of the cytokines known to prolong the survival of osteoclasts, such as IL-1beta, TNF-alpha, and receptor activator of NF-kappaB ligand. LPS stimulated the production of proinflammatory cytokines such as IL-1beta, TNF-alpha, and IL-6 in bone marrow macrophages and peritoneal macrophages, but not in osteoclasts. These results indicate that osteoclasts respond to LPS through TLR4, but the characteristics of osteoclasts are quite different from those of their precursors, macrophages, in terms of proinflammatory cytokine production in response to LPS.