Overexpression of hepatic serum amyloid A1 in mice increases IL-17-producing innate immune cells and decreases bone density.
Overexpression of hepatic serum amyloid A1 in mice increases IL-17-producing innate immune cells and decreases bone density.
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DOI：
10.1016/j.jbc.2021.100595
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Choi SK
中科院分区：
文献类型：
--
作者：
Choi M;Park S;Yi JK;Kwon W;Jang S;Kim SY;Yu W;Kim MO;Ryoo ZY;Choi SK
血清淀粉样蛋白A（SAA）是一种急性期蛋白，主要在肝脏中产生，在炎症的启动和维持中起关键作用。快速分泌的SAA在炎症部位诱导嗜中性粒细胞，引发炎症并诱导各种细胞因子的分泌，包括TNF-α、IL-6和IL-17。IL-17在几种炎性细胞中表达，包括先天性免疫细胞如γδT细胞、ILC 3细胞和嗜中性粒细胞。IL-17水平的增加加剧了各种炎症性疾病。在其他作用中，IL-17通过增加刺激破骨细胞分化的核因子-κB配体（RANKL）的受体激活剂分泌来诱导骨丢失。一些研究表明，慢性炎症会导致骨质流失，这表明SAA在骨骼健康中的作用。为了测试这种可能性，我们观察到这些小鼠中产生IL-17的先天免疫细胞、中性粒细胞和γδT细胞的增加。在6个月大的动物中，我们检测到破骨细胞相关基因表达和骨溶解物中IL-17表达增加。我们还观察到TG小鼠骨髓中分泌RANKL的中性粒细胞增加。最后，我们证明了这些转基因（TG）小鼠的骨密度降低。我们的结果显示，TG小鼠中产生IL-17的先天免疫细胞、γδT细胞和中性粒细胞的数量增加。我们还检测到6月龄TG小鼠骨髓中RANKL和IL-17表达增加。此外，我们证实TG小鼠中RANKL表达的中性粒细胞显著增加，骨密度降低。我们的研究结果提供了证据表明，SAA 1诱导的慢性炎症通过分泌IL-17的先天免疫细胞引起骨丢失。
Serum amyloid A (SAA) is an acute-phase protein produced primarily in the liver that plays a key role in both the initiation and maintenance of inflammation. Rapidly secreted SAA induces neutrophilia at inflammatory sites, initiating inflammation and inducing the secretion of various cytokines, including TNF-α, IL-6, and IL-17. IL-17 is expressed in several inflammatory cells, including innate immune cells such as γδT cells, ILC3 cells, and neutrophils. Increased IL-17 levels exacerbate various inflammatory diseases. Among other roles, IL-17 induces bone loss by increasing receptor activator of nuclear factor-κB ligand (RANKL) secretion, which stimulates osteoclast differentiation. Several studies have demonstrated that chronic inflammation induces bone loss, suggesting a role for SAA in bone health. To test this possibility, we observed an increase in IL-17-producing innate immune cells, neutrophils, and γδT cells in these mice. In 6-month-old animals, we detected increased osteoclast-related gene expression and IL-17 expression in bone lysates. We also observed an increase in neutrophils that secreted RANKL in the bone marrow of TG mice. Finally, we demonstrated decreased bone mineral density in these transgenic (TG) mice. Our results revealed that the TG mice have increased populations of IL-17-producing innate immune cells, γδT cells, and neutrophils in TG mice. We additionally detected increased RANKL and IL-17 expression in the bone marrow of 6-month-old TG mice. Furthermore, we confirmed significant increases in RANKL-expressing neutrophils in TG mice and decreased bone mineral density. Our results provide evidence that chronic inflammation induced by SAA1 causes bone loss via IL-17-secreting innate immune cells.
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DOI：
10.2741/4214
发表时间：
2014-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Wang Y;Li YP;Paulson C;Shao JZ;Zhang X;Wu M;Chen W
通讯作者：
Chen W
影响因子：
64.5
作者：
Sano T;Huang W;Hall JA;Yang Y;Chen A;Gavzy SJ;Lee JY;Ziel JW;Miraldi ER;Domingos AI;Bonneau R;Littman DR
通讯作者：
Littman DR
尖端：TLR2是急性阶段血清淀粉样蛋白A的功能受体。
DOI：
10.4049/jimmunol.181.1.22
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cheng N;He R;Tian J;Ye PP;Ye RD
通讯作者：
Ye RD
炎性关节炎需要中性粒细胞的白细胞B4。
DOI：
10.1084/jem.20052371
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Jang, Woo Young;Jeong, Jain;Ryoo, Zae Young
通讯作者：
Ryoo, Zae Young