title: The insect peptide CopA3 inhibits lipopolysaccharide-induced macrophage activation.
abstract: We recently demonstrated that the insect peptide CopA3 (LLCIALRKK), a disulfide-linked dimeric peptide, exerts antimicrobial and anti-inflammatory activities in a mouse colitis model. Here, we examined whether CopA3 inhibited activation of macrophages by LPS. Exposure of an unseparated mouse peritoneal cell population or isolated peritoneal macrophages to LPS markedly increased secretion of IL-6 and TNF-α; these effects were significantly inhibited by CopA3 treatment. The inhibitory effect of CopA3 was also evident in murine macrophage cell line, RAW 264.7. Western blotting revealed that LPS-induced activation of STAT1 and STAT5 in macrophages was significantly inhibited by CopA3. Inhibition of JAK (STAT1/STAT5 kinase) with AG490 markedly reduced the production of IL-6 and TNF-α in macrophages. Collectively, these observations suggest that CopA3 inhibits macrophage activation by inhibiting activating phosphorylations of the transcription factors, STAT1 and STAT5, and blocking subsequent production of IL-6 and TNF-α and indicate that CopA3 may be useful as an immune-modulating agent.
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido, South Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Nam
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Oh
authors.forename: Seung Taek
authors.initials: ST
authors.lastname: Nam
authors.forename: Jin Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Chang
authors.forename: Dae Hong
authors.initials: DH
authors.lastname: Kim
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Lee
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
authors.forename: Ko Eun
authors.initials: KE
authors.lastname: Shong
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Heon
authors.initials: H
authors.lastname: Seok
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019476:Insect Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007313:Insecta / Q000737:chemistry*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D050794:STAT1 Transcription Factor; D050799:STAT5 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C570442:coprisin peptide, Copris tripartitus