The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors.
The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors.
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抗菌肽组织蛋白酶抑制素通过清道夫受体发挥免疫调节作用。
DOI：
10.3390/ijms24010875
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发表时间：
2023-01-03
影响因子：
5.6
通讯作者：
Asano, Yoshihide
中科院分区：
文献类型：
--
作者：
Amagai, Ryo;Takahashi, Toshiya;Terui, Hitoshi;Fujimura, Taku;Yamasaki, Kenshi;Aiba, Setsuya;Asano, Yoshihide
关键词：
抗菌肽的活性形式LL-37具有免疫调节和刺激作用，但具体途径尚不清楚。本研究的目的是确定LL-37放大由损伤相关分子模式（DAMPs）诱导的炎症的细胞途径。我们使用LL-37和/或DAMP poly(I:C)（一种合成的双链RNA）处理的培养角质形成细胞进行了DNA微阵列、逆转录聚合酶链反应、免疫印迹和近距离连接试验。与LL-37和poly（I:C）的组合相比，LL-37单独诱导了VEGFA和PTGS2 （COX-2）等与生物代谢过程相关的基因。抑制FPR2（一种已知的cathelicidin受体）部分抑制VEGFA和PTGS2的诱导。重要的是，单独由LL-37诱导的VEGFA和PTGS2通过敲低清道夫受体包括SCARB1 (SR-B1), OLR1 （SR-E1）和AGER （SR-J1）而减少。此外，LL-37单独以及LL-37与poly（I:C）的组合均表现出与清道夫受体的接近性，表明LL-37通过清道夫受体及其与poly（I:C）之间的中间体起作用。这些结果表明，抗菌肽的广泛功能通常依赖于清道夫受体。因此，清道夫受体抑制剂或无功能模拟抗菌肽可能作为新的抗炎和免疫抑制剂。
An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents.
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RIG-I 样受体的免疫信号传导。
影响因子：
32.4
作者：
Loo YM;Gale M Jr
通讯作者：
Gale M Jr
DOI：
10.1073/pnas.91.23.11035
发表时间：
1994-11-08
影响因子：
11.1
作者：
GALLO, RL;ONO, M;BERNFIELD, M
通讯作者：
BERNFIELD, M
影响因子：
8
作者：
Li, D.;Beisswenger, C.;Bals, R.
通讯作者：
Bals, R.
影响因子：
6.5
作者：
Kulkarni, Nikhil N.;Takahashi, Toshiya;Sanford, James A.;Tong, Yun;Gombart, Adrian F.;Hinds, Brian;Cheng, Joyce Y.;Gallo, Richard L.
通讯作者：
Gallo, Richard L.
影响因子：
13.6
作者：
Benhadou, Farida;Glitzner, Elisabeth;Blanpain, Cedric
通讯作者：
Blanpain, Cedric