Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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An Analog of the Antimicrobial Peptide CopA5 Inhibits Lipopolysaccharide-Induced Macrophage Activation

  • Yoon, I Na (Divison of Life Science and Chemistry, College of Natural Science, Daejin University) ;
  • Hong, Ji (Divison of Life Science and Chemistry, College of Natural Science, Daejin University) ;
  • Zhang, Peng (Divison of Life Science and Chemistry, College of Natural Science, Daejin University) ;
  • Hwang, Jae Sam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Kim, Ho (Divison of Life Science and Chemistry, College of Natural Science, Daejin University)
  • Received : 2016.07.28
  • Accepted : 2016.10.11
  • Published : 2017.02.28
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Abstract

We previously reported that the CopA3 peptide (LLCIALRKK, ${\small{D}}-form$) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the ${\small{D}}-form$, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the ${\small{L}}-form$ structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages. Peritoneal exudate macrophages (PEM) were isolated from mice and exposed to LPS in the presence or absence of CopA5, and biomarkers of macrophage activation were measured. Our results revealed that LPS-induced nitric oxide (NO) production, tumor necrosis factor $(TNF)-{\alpha}$ secretion, and phagocytic activity of PEM were significantly inhibited by CopA5 treatment. Similar to CopA3, the structurally modified CopA5 peptide had no cell toxicity (as assessed by measurement of cell viability loss and apoptosis) in PEM. Moreover, the LPS-induced upregulation of the activating phosphorylation of signal transducer and activator of transcription 1 (STAT1) was markedly inhibited by CopA5 treatment. These results suggest that, similar to CopA3, CopA5 inhibits macrophage activation by inhibiting STAT1 phosphorylation and blocking the release of NO and $TNF-{\alpha}$. CopA5 may therefore prove therapeutically useful in the realm of immune suppression.

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References

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