Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1–6) were identified and characterized from the endangered Chinese alligator (Alligator sinensis). As-CATH1–6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1–3 adopt a random coil secondary conformation, whereas As-CATH4–6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4–6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4–6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2–6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1–6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1–6 partially reveal the powerful immune system of the Chinese alligator.
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August 2017
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The distribution of haemagglutinin (green) and β-catenin (red) in MDCK cells overexpressing Akt1-HA. In this issue of the Biochemical Journal, Castañeda et al. report on the suppression of Akt/β-catenin-mediated cell proliferation by the the inhibition of 14-3-3ζ expression (see pages 2679–2689).
Research Article|
August 10 2017
As-CATH1–6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses
Yan Chen;
Yan Chen
*
1Department of Pharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
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Shasha Cai;
Shasha Cai
*
2Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China
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Xue Qiao;
Xue Qiao
2Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China
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Mali Wu;
Mali Wu
3Guizhou Province Center of Disease Control and Protection, Guiyang, Guizhou 550004, China
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Zhilai Guo;
Zhilai Guo
4Biology Department, Guizhou Normal University, Guiyang, Guizhou 550000, China
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Renping Wang;
Renping Wang
5Anhui Chinese Alligator National Nature Reserve, Xuancheng, Anhui 242034, China
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Yi-Qun Kuang;
Yi-Qun Kuang
6Center for Translational Medicine, Huaihe Clinical College, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, China
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Haining Yu;
2Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning 116023, China
Correspondence: Yipeng Wang (yipengwang@suda.edu.cn) or Haining Yu (yuhaining@dlut.edu.cn)
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Yipeng Wang
1Department of Pharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China
Correspondence: Yipeng Wang (yipengwang@suda.edu.cn) or Haining Yu (yuhaining@dlut.edu.cn)
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Publisher: Portland Press Ltd
Received:
May 04 2017
Revision Received:
July 12 2017
Accepted:
July 17 2017
Accepted Manuscript online:
July 18 2017
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem J (2017) 474 (16): 2861–2885.
Article history
Received:
May 04 2017
Revision Received:
July 12 2017
Accepted:
July 17 2017
Accepted Manuscript online:
July 18 2017
Citation
Yan Chen, Shasha Cai, Xue Qiao, Mali Wu, Zhilai Guo, Renping Wang, Yi-Qun Kuang, Haining Yu, Yipeng Wang; As-CATH1–6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses. Biochem J 15 August 2017; 474 (16): 2861–2885. doi: https://doi.org/10.1042/BCJ20170334
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