Expression of Fgf23 in Activated Dendritic Cells and Macrophages in Response to Immunological Stimuli in Mice
Expression of Fgf23 in Activated Dendritic Cells and Macrophages in Response to Immunological Stimuli in Mice
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DOI：
10.1248/bpb.b14-00276
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发表时间：
2015-05-01
影响因子：
2
通讯作者：
Konishi, Morichika
中科院分区：
文献类型：
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作者：
Masuda, Yuki;Ohta, Hiroya;Konishi, Morichika
成纤维细胞生长因子（Fibroblast growth factors，Fgfs）是一类具有多种生物学活性的多肽生长因子。虽然一些研究表明Fgf 23在磷酸盐和维生素D代谢的调节中起重要作用，但Fgf 23的其他生理作用仍不清楚。尽管我们认为成骨细胞/骨细胞是Fgf 23的主要来源，但我们先前发现Fgf 23 mRNA也在小鼠胸腺中表达，这表明它可能参与免疫系统。在这项研究中，我们研究了Fgf 23在免疫应答中的潜在作用。小鼠血清Fgf 23水平显着增加接种大肠杆菌或金黄色葡萄球菌或腹腔注射脂多糖。我们还鉴定了活化的树突状细胞和巨噬细胞，它们可能导致血清Fgf 23水平升高。核因子-κ B（NF-κ B）信号传导对于响应免疫刺激的树突状细胞中Fgf 23表达的诱导是必不可少的。此外，我们研究了重组Fgf 23蛋白对体外免疫细胞的影响。Fgfr 1c是Fgf 23的潜在受体，在巨噬细胞中大量表达，表明Fgf 23可能参与这些细胞中的信号转导。我们的数据表明，Fgf 23可能增加巨噬细胞的数量，并诱导肿瘤坏死因子-α（TNF-α），一种促炎细胞因子的表达。总的来说，这些数据表明Fgf 23可能密切参与炎症过程。
Fibroblast growth factors (Fgfs) are polypeptide growth factors with diverse biological activities. While several studies have revealed that Fgf23 plays important roles in the regulation of phosphate and vitamin D metabolism, the additional physiological roles of Fgf23 remain unclear. Although it is believed that osteo-blasts/osteocytes are the main sources of Fgf23, we previously found that Fgf23 mRNA is also expressed in the mouse thymus, suggesting that it might be involved in the immune system. In this study we examined the potential roles of Fgf23 in immunological responses. Mouse serum Fgf23 levels were significantly increased following inoculation with Escherichia coli or Staphylococcus aureus or intraperitoneal injection of lipopolysaccharide. We also identified activated dendritic cells and macrophages that potentially contributed to increased serum Fgf23 levels. Nuclear factor-kappa B (NF-kappa B) signaling was essential for the induction of Fgf23 expression in dendritic cells in response to immunological stimuli. Moreover, we examined the effects of recombinant Fgf23 protein on immune cells in vitro. Fgfr1c, a potential receptor for Fgf23, was abundantly expressed in macrophages, suggesting that Fgf23 might be involved in signal transduction in these cells. Our data suggest that Fgf23 potentially increases the number in macrophages and induces expression of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine. Collectively, these data suggest that Fgf23 might be intimately involved in inflammatory processes.