In human macrophages the complement component C5a induces the expression of oncostatin M via AP-1 activation
In human macrophages the complement component C5a induces the expression of oncostatin M via AP-1 activation
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DOI：
10.1161/atvbaha.107.160580
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发表时间：
2008-03-01
影响因子：
8.7
通讯作者：
Wojta, Johann
中科院分区：
文献类型：
--
作者：
Kastl, Stefan P.;Speidl, Walter S.;Wojta, Johann
目的-巨噬细胞产生细胞因子抑瘤素M（oncostatin M，OSM），除了其他功能外，还参与炎症反应.补体成分C5 a动员并激活炎症部位的这些细胞。我们研究了C5 a对人单核细胞和人单核细胞衍生的巨噬细胞中OSM产生的影响。方法和结果-对于巨噬细胞转化，将外周血单核细胞在人血清存在下培养8至10天。C5 a在这些细胞中显著增加，如通过特异性ELISA测定的OSM抗原和如通过实时聚合酶链反应定量的mRNA在这些细胞中以及在斑块巨噬细胞中。这种作用被针对受体C5 aR/CD 88的抗体和百日咳毒素阻断。C5 a诱导的p38和JNK磷酸化以及C5 a诱导的巨噬细胞中OSM产生的增加被2种p38抑制剂和JNK抑制剂消除。此外，C5 a增加了c-fos和c-jun的核转位。使用不同的OSM启动子缺失突变体构建体，我们表明假定的AP-1元件负责C5 a激活OSM启动子活性。结论-我们的数据建立了补体系统和gp 130受体细胞因子家族之间的联系，可能对炎症性疾病的病理学有影响。
Objective - Macrophages produce the cytokine oncostatin M (OSM), which beside other functions is also involved in inflammation. The complement component C5a mobilizes and activates these cells at inflammatory sites. We examined the effect of C5a on OSM production in human monocytes and in human monocyte-derived macrophages.Methods and Results - For macrophage transformation peripheral blood monocytes were cultivated for 8 to 10 days in the presence of human serum. C5a significantly increased in these cells OSM antigen as determined by specific ELISA and mRNA as quantitated by real-time polymerase chain reaction in these cells as well as in plaque macrophages. This effect was blocked by antibodies against the receptor C5aR/CD88 and by pertussis toxin. The C5a-induced phosphorylation of p38 and JNK and the C5a-induced increase in OSM production in macrophages was abolished by 2 p38 inhibitors and by a JNK inhibitor. Furthermore C5a increased the nuclear translocation of c-fos and c-jun. Using different OSM promoter deletion mutant constructs we show that the putative AP-1 element is responsible for activation of OSM promoter activity by C5a.Conclusion - Our data establish a link between the complement system and the gp130 receptor cytokine family with possible implications for the pathology of inflammatory diseases.