LL-37抑制血清淀粉样蛋白A诱导的人中性粒细胞产生白细胞介素-8。
LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils.
作者信息
Lee Ha Young, Kim Sang Doo, Shim Jae Woong, Lee Sun Young, Yun Jeanho, Bae Yoe-Sik
机构信息
Department of Biochemistry, Dong-A University, Busan, Korea.
出版信息
Exp Mol Med. 2009 May 31;41(5):325-33. doi: 10.3858/emm.2009.41.5.036.
Abstract
Serum amyloid A (SAA) has been regarded as an important mediator of inflammatory responses. The effect of several formyl peptide receptor-like 1 (FPRL1) ligands on the production of IL-8 by SAA was investigated in human neutrophils. Among the ligands tested, LL-37 was found to specifically inhibit SAA-induced IL-8 production in transcriptional and post-transcriptional levels. Since SAA stimulated IL-8 production via ERK and p38 MAPK in human neutrophils, we tested the effect of LL-37 on SAA induction for these two MAPKs. LL-37 caused a dramatic inhibition of ERK and p38 MAPK activity, which is induced by SAA. LL-37 was also found to inhibit SAA-stimulated neutrophil chemotactic migration. Further, the LL-37-induced inhibitory effect was mediated by FPRL1. Our findings indicate that LL-37 is expected to be useful in the inhibition of SAA signaling and for the development of drugs against SAA-related inflammatory diseases.
摘要
血清淀粉样蛋白A（SAA）被认为是炎症反应的重要介质。在人类中性粒细胞中研究了几种类甲酰肽受体1（FPRL1）配体对SAA诱导白细胞介素-8（IL-8）产生的影响。在测试的配体中，LL-37被发现可在转录和转录后水平特异性抑制SAA诱导的IL-8产生。由于SAA在人类中性粒细胞中通过细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶（MAPK）刺激IL-8产生，我们测试了LL-37对这两种MAPK的SAA诱导作用的影响。LL-37对SAA诱导的ERK和p38 MAPK活性产生显著抑制。还发现LL-37可抑制SAA刺激的中性粒细胞趋化迁移。此外，LL-37诱导的抑制作用由FPRL1介导。我们的研究结果表明，LL-37有望用于抑制SAA信号传导以及开发针对SAA相关炎症性疾病的药物。
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