Department of Biochemistry and Molecular Biology, Wright State University School Medicine, Dayton, OH 45435, USA.
FEBS Lett. 2011 Jan 3;585(1):159-66. doi: 10.1016/j.febslet.2010.11.031. Epub 2010 Nov 21.
Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase vital to the regulation of T-cells. We report that JAK3 is a mediator of interleukin-8 (IL-8) stimulation of a different class of hematopoietic relevant cells: human neutrophils. IL-8 induced a time- and concentration-dependent activation of JAK3 activity in neutrophils and differentiated HL-60 leukemic cells. JAK3 was more robustly activated by IL-8 than other kinases: p70S6K, mTOR, MAPK or PKC. JAK3 silencing severely inhibited IL-8-mediated chemotaxis. Thus, IL-8 stimulates chemotaxis through a mechanism mediated by JAK3. Further, JAK3 activity and chemotaxis were inhibited by the flavonoid apigenin (4',5,7-trihydroxyflavone) at ∼5nM IC(50). These new findings lay the basis for understanding the molecular mechanism of cell migration as it relates to neutrophil-mediated chronic inflammatory processes.
Janus 激酶 3（JAK3）是一种非受体酪氨酸激酶，对 T 细胞的调节至关重要。我们报告称，JAK3 是白细胞介素-8（IL-8）刺激另一类造血相关细胞（人中性粒细胞）的介质。IL-8 诱导中性粒细胞和分化的 HL-60 白血病细胞中 JAK3 活性的时间和浓度依赖性激活。与其他激酶（p70S6K、mTOR、MAPK 或 PKC）相比，JAK3 被 IL-8 更强烈地激活。JAK3 沉默严重抑制了 IL-8 介导的趋化作用。因此，IL-8 通过 JAK3 介导的机制刺激趋化作用。此外，黄酮类化合物芹菜素（4'，5，7-三羟基黄酮）在约 5nM IC（50）时抑制 JAK3 活性和趋化作用。这些新发现为理解与中性粒细胞介导的慢性炎症过程相关的细胞迁移的分子机制奠定了基础。
