Host defense peptide LEAP-2 contributes to monocyte/macrophage polarization in barbel steed (Hemibarbus labeo)
Host defense peptide LEAP-2 contributes to monocyte/macrophage polarization in barbel steed (Hemibarbus labeo)
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DOI：
10.1016/j.fsi.2019.01.015
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发表时间：
2019-04-01
影响因子：
4.7
通讯作者：
Li, Ji-Heng
中科院分区：
文献类型：
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作者：
Chen, Jie;Lv, Yao-Ping;Li, Ji-Heng
肝脏表达的抗菌肽2 （LEAP-2）在宿主对病原生物的免疫中起着至关重要的作用。本研究从棘马（Hemibarbus labeo）中克隆了LEAP-2基因cDNA并进行了测序。预测的倒钩钢LEAP-2的氨基酸序列包括一个信号肽和一个前结构域，然后是成熟肽。序列分析表明，棘鱼LEAP-2属于鱼类LEAP-2A簇，与斑马鱼LEAP-2A亲缘关系较近。我们发现倒刺马的LEAP-2转录本在广泛的组织中表达，在肝脏中检测到最高的mRNA水平。在脂多糖（LPS）处理下，LEAP-2在肝脏、头肾、脾脏、鳃和中肠中显著上调。化学合成的LEAP-2成熟肽对几种细菌具有选择性抗菌活性。此外，LEAP-2单独或与LPS或phorbol 12-肉豆酸酯13-醋酸酯联合使用，强烈诱导了刺钢单核/巨噬细胞（MO/M Phi）的促炎反应，包括诱导iNOS活性、呼吸爆发和促炎细胞因子ifn - γ、tnf - α和IL-1 β。综上所述，本研究结果表明了鱼类LEAP-2在MO/M Phi的ml型极化中的重要性。
The liver-expressed antimicrobial peptide 2 (LEAP-2) plays a vital role in host immunity against pathogenic organisms. In the present study, cDNA of the LEAP-2 gene was cloned and sequenced from the barbel steed (Hemibarbus labeo). The predicted amino acid sequence of the barbel steed LEAP-2 comprises a signal peptide and a prodomain, which is followed by the mature peptide. Sequence analysis revealed that barbel steed LEAP-2 belongs to the fish LEAP-2A cluster and that it is closely related to zebrafish LEAP-2A. We found that barbel steed LEAP-2 transcripts were expressed in a wide range of tissues, with the highest mRNA levels detected in the liver. In response to lipopolysaccharide (LPS) treatment, LEAP-2 was significantly upregulated in the liver, head kidney, spleen, gill, and mid intestine. A chemically synthesized LEAP-2 mature peptide exhibited selective antimicrobial activity against several bacteria in vitro. Moreover, LEAP-2, alone or in combination with LPS or phorbol 12-myristate 13-acetate, strongly induced a pro-inflammatory reaction in barbel steed monocytes/macrophages (MO/M Phi), involving the induction of iNOS activity, respiratory burst, and the pro-inflammatory cytokines IFN-gamma, TNF-alpha, and IL-1 beta. Collectively, the results of this study indicate the importance of fish LEAP-2 in the Ml-type polarization of MO/M Phi.