Bv8, the amphibian homologue of the mammalian prokineticins, induces a proinflammatory phenotype of mouse macrophages
Bv8, the amphibian homologue of the mammalian prokineticins, induces a proinflammatory phenotype of mouse macrophages
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DOI：
10.1038/sj.bjp.0706467
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发表时间：
2006-01-01
影响因子：
7.3
通讯作者：
Sacerdote, P
中科院分区：
文献类型：
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作者：
Martucci, C;Franchi, S;Sacerdote, P
从两栖动物皮肤中分离出的小蛋白Bv 8属于一个与多种生物学效应相关的新型分泌蛋白家族。我们描述了小鼠巨噬细胞中Bv 8/prokineticins及其受体的表达，并表征了其促炎活性。2 Bv 8的啮齿动物类似物prokineticin-2由巨噬细胞及其G蛋白偶联受体prokineticin受体（PKR-1和PKR-2）表达。PKR-1表达更丰富。3 Bv 8在低至10（-12）M的浓度下诱导巨噬细胞的强效趋化性。4它刺激脂多糖诱导的促炎细胞因子IL-1和IL-12的产生，减少抗炎细胞因子IL-10的产生。从10（-11）M的极低浓度开始观察到这些作用。5对趋化性和细胞因子的作用对百日咳毒素不敏感，但通过加入磷脂酶抑制剂U 73122可完全阻止，这表明G（q）蛋白参与Bv 8诱导的效应。6 PKR研究-1基因敲除小鼠的研究表明，Bv 8对巨噬细胞的所有活性都是由PKR-1受体介导的。7总之，Bv 8似乎能够诱导巨噬细胞迁移并获得促炎表型。
1 The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities.2 The rodent analogue of Bv8, prokineticin-2, is expressed by macrophages, as well as its G-protein-coupled receptor prokineticin receptor (PKR-1 and PKR-2). PKR-1 is expressed more abundantly.3 Bv8 induces potent chemotaxis of macrophages at concentrations as low as 10(-12) M.4 It stimulates lipopolysaccharide-induced production of the proinflammatory cytokines IL-1 and IL-12, reducing that of the anti-inflammatory cytokine IL-10. The effects are observed starting at the very low concentration of 10(-11) M.5 Effects on chemotaxis and cytokine are not pertussis-toxin sensitive, but are completely prevented by addition of the phospholipase inhibitor U73122, suggesting a G(q) protein is involved in the Bv8-induced effects.6 Studies in PKR-1 knockout mice indicate that all the activities exerted by Bv8 on macrophages are mediated by the PKR-1 receptor. 7 In conclusion, Bv8 appears to be able to induce the macrophage to migrate and to acquire a proinflammatory phenotype.