Synthetic chemerin-derived peptides suppress inflammation through ChemR23.
Synthetic chemerin-derived peptides suppress inflammation through ChemR23.
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DOI：
10.1084/jem.20071601
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发表时间：
2008-04-14
影响因子：
15.3
通讯作者：
Greaves, David R.
中科院分区：
文献类型：
--
作者：
Cash, Jenna L.;Hart, Rosie;Russ, Andreas;Dixon, John P. C.;Colledge, William H.;Doran, Joanne;Hendrick, Alan G.;Carlton, Mark B. L.;Greaves, David R.
Chemerin是一种与G蛋白偶联受体ChemR 23结合的趋化蛋白。我们证明，小鼠chemerin具有强大的生物学特性，是绝对依赖于蛋白水解加工。设计了一系列的肽，只有那些相同的特定的C-末端chemerin序列在皮摩尔浓度在体外发挥抑制作用。其中之一chemerin 15（C15; A140-A154）抑制巨噬细胞（MΦ）活化的程度与蛋白水解chemerin相似，但作为MΦ化学引诱物的活性降低。在酵母多糖攻击前向小鼠腹膜内施用C15（0.32 ng/kg）赋予对酵母多糖诱导的腹膜炎的显著保护，抑制中性粒细胞（63%）和单核细胞（62%）募集，伴随着促炎介质表达的减少。重要的是，C15不能改善ChemR 23 −/−小鼠中酵母聚糖诱导的腹膜炎，表明C15的抗腹膜炎作用完全依赖于ChemR 23。此外，酵母多糖攻击前给予中和抗chemerin抗体导致腹膜炎症显著加重（高达170%），表明chemerin衍生物种的重要内源性抑制作用。总的来说，这些结果表明，chemerin衍生的肽可能代表了一种新的治疗策略，通过ChemR 23治疗炎症性疾病。
Chemerin is a chemotactic protein that binds to the G protein–coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A140-A154), inhibited macrophage (MΦ) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MΦ chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23−/− mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23.
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影响因子：
4.8
作者：
Wittamer, V;Grégoire, F;Parmentier, M
通讯作者：
Parmentier, M
DOI：
10.1073/pnas.0710487105
发表时间：
2008-01-08
影响因子：
11.1
作者：
Barnea, Gilad;Strapps, Walter;Lee, Kevin J.
通讯作者：
Lee, Kevin J.
影响因子：
4.4
作者：
Arita, Makoto;Ohira, Taisuke;Serhan, Charles N.
通讯作者：
Serhan, Charles N.
影响因子：
7.3
作者：
Getting, SJ;Flower, RJ;Perretti, M
通讯作者：
Perretti, M
影响因子：
3.5
作者：
Meder, W;Wendland, M;Forssmann, WG
通讯作者：
Forssmann, WG