Department of Microbiology and Immunology, University of South China, Hengyang Hunan, China.
J Interferon Cytokine Res. 2011 May;31(5):415-22. doi: 10.1089/jir.2010.0094. Epub 2011 Feb 3.
Interleukin-1 receptor-associated kinase 2 (IRAK2) has been shown to be essential for lipopolysaccharide (LPS)-mediated posttranscriptional control of cytokine and chemokine production. In this study, we investigated the role of IRAK2 kinase activity in LPS-mediated posttranscriptional control by reconstituting IRAK2-deficient macrophages with either wild-type or kinase-inactive IRAK2. Compared with wild-type IRAK2 (IRAK2-WT) macrophages, kinase-inactive IRAK2 (IRAK2-KD) macrophages show reduced cytokine and chemokine mRNA stability and translation in response to LPS. Further, LPS-treated IRAK2-KD macrophages also show reduced activation of MKK3/6, MNK1, and eIF4E and attenuated toll-like receptor 4-induced tristetraprolin modification and stabilization. Taken together, these results suggest that the kinase activity of IRAK2 is required for the optimal activation of mitogen-activated protein kinase signaling, which regulates cytokine and chemokine production at posttranscriptional levels.
白介素-1 受体相关激酶 2（IRAK2）已被证明对于脂多糖（LPS）介导的细胞因子和趋化因子产生的转录后控制至关重要。在这项研究中，我们通过用野生型或激酶失活的 IRAK2 重建 IRAK2 缺陷型巨噬细胞，研究了 IRAK2 激酶活性在 LPS 介导的转录后控制中的作用。与野生型 IRAK2（IRAK2-WT）巨噬细胞相比，激酶失活的 IRAK2（IRAK2-KD）巨噬细胞在 LPS 刺激下表现出细胞因子和趋化因子 mRNA 稳定性和翻译的降低。此外，LPS 处理的 IRAK2-KD 巨噬细胞还显示出 MKK3/6、MNK1 和 eIF4E 的激活减少，以及 Toll 样受体 4 诱导的 tristetraprolin 修饰和稳定作用减弱。总之，这些结果表明 IRAK2 的激酶活性对于丝裂原活化蛋白激酶信号的最佳激活是必需的，该激酶在转录后水平调节细胞因子和趋化因子的产生。
