The role of IL-18 in bone destruction due to cancer metastasis

1. IL-18在转移性肿瘤骨吸收中的作用：（1）成骨细胞和破骨细胞IL-18受体的表达：免疫组化法检测成骨细胞和破骨细胞IL-18受体的表达。逆转录酶聚合酶链反应也在这些细胞中表达了IL-18受体成分mRNA的存在。(2)IL-18在体外条件下骨细胞骨吸收中的作用：从小鼠纯化的骨细胞骨吸收在与IL-18共培养中受到抑制。(3)IL-18在体内骨转移中的作用：采用裸鼠心腔内注射人乳腺癌细胞（MDA-231）和骨髓瘤细胞（ARH-77）建立骨转移模型。IL-18抑制骨转移部位的癌的溶骨性生长。(4)IL-18抑制骨破坏的机制：IL-12可协同增强IL-18抑制骨破坏的作用，随后产生干扰素γ（IFN-γ）. IL-18在骨关节炎（OA）和类风湿性关节炎（RA）发病机制中的作用。(1)IL-18在OA软骨降解中的作用：OA滑液中IL-18与前列腺素E^2存在较强的相关性，IL-18通过释放PGE^2在OA的发病机制中起重要作用。(2)RA中IL-18的产生：IL-18已被报道为类风湿性关节炎（RA）中的促炎细胞因子。我们通过可溶性Fas配体刺激CD 14+巨噬细胞释放IL-18来检测IL-18的释放。总之，靶向IL-18似乎是一种重要的治疗方法，可以防止骨转移瘤、OA和RA等疾病的骨破坏和关节软骨退化。

1. The role of Interleukin (IL)-18 in bone resorption due to metastatic cancer :(1) Expression of IL-18 receptor in osteoblast and osteoclast : IL-18 receptor was detected in both osteoblast and osteoclast by immunohistochemical technique. The presence of mRNAs for IL-18 receptor components was also expressed by reverse transcriptase polymerase chain reaction in these cells.(2) The role of IL-18 in osteoclastic bone resporption in vitro condition : Osteoclastic bone resorption, purified from mice, was inhibited in co-culture with IL-18.(3) The role of IL-18 in osteoclastic bone resporption in vivo condition : The model of bone metastasis was established by an intracardiac injection of human breast cancer cells (MDA-231) and myeloma cell (ARH-77) in nude mice. IL-18 inhibited osteolytic growth of the cancer at bone metastatic sites.(4) The mechanism of the suppression of bone destruction by IL-18 : This activity could be synergistically enhanced by IL-12 followed by interferon gamma (IFN-γ) production.2. The role of IL-18 in pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA).(1) The role of IL-18 in cartilage degradation of OA : There was a relatively strong correlation of IL-18 to prostaglandin (PG)E^2 in the synovial fluid of OA.IL-18 plays an important role in the pathogenesis of OA through the PGE^2 release.(2) Production of IL-18 in RA : IL-18 has been reported as a proinflammatory cytokine in rheumatoid arthritis (RA). We determined the IL-18 release in CD14+ macrophages by stimulation of soluble Fas ligand.In conclusion, targeting the IL-18 appears to be an important therapeutic approach to prevent bone destruction and articular cartilage degradation, in diseases such as metastatic bone tumor, OA, and RA.