Interleukin-1 receptor associated kinase 1 is a potential therapeutic target of anti-inflammatory therapy for systemic lupus erythematosus
Interleukin-1 receptor associated kinase 1 is a potential therapeutic target of anti-inflammatory therapy for systemic lupus erythematosus
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IL-1受体相关激酶1是系统性红斑狼疮抗炎治疗的潜在治疗靶点
DOI：
10.1016/j.molimm.2017.03.018
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发表时间：
2017-07-01
影响因子：
3.6
通讯作者：
Hao, Fei
中科院分区：
文献类型：
--
作者：
Li, Mingfang;Yu, Datang;Hao, Fei
系统性红斑狼疮（SLE）是一种慢性自身免疫性炎症性疾病，目前尚无有效的治疗方法。全基因组分析表明，白细胞介素-1受体相关激酶1（IRAK 1）与人类SLE的易感性有关。在本研究中，我们确定IRAK 1在B6.MRL-Fas（lPr）/Nju（B6. lpr）小鼠的脾单个核细胞和SLE患者的外周血单个核细胞（PBMC）中过表达和过度活化。用IRAK 1的小分子抑制剂（IRAK 1/4抑制剂或IRAK-Inh）腹膜内治疗显著减轻B6.lpr小鼠的炎症反应和肾损伤。IRAK-Inh治疗或通过特异性siRNA敲低IRAK 1降低SLE患者人PBMC中NF-κ Bp 65磷酸化的相对水平。因此，IRAK 1可能成为SLE等炎症性疾病抗炎治疗的潜在靶点。(C)2017爱思唯尔有限公司版权所有
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas(lPr)/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6.lpr mice. IRAK-Inh treatment or knockdown of IRAK1 by specific siRNA decreased the relative levels of NF-kappa Bp65 phosphorylation in human PBMCs from SLE patients. Therefore, IRAK1 may be a potential target for anti-inflammatory therapy for SLE and other inflammatory diseases. (C) 2017 Elsevier Ltd. All rights reserved.