The insect peptide CopA3 inhibits lipopolysaccharide‐induced macrophage activation

Nam, Hyo Jung; Oh, Ah Reum; Nam, Seung Taek; Kang, Jin Ku; Chang, Jen-Yuan; Kim, Dae Hong; Lee, Ji Hye; Hwang, Jae Sam; Shong, Ko Eun; Park, Mi Jung; Seok, Heon; Kim, Ho

doi:10.1002/psc.2437

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…Zhu et al reported that GNPs significantly attenuated the rise in ROS/RNS-mediated inflammatory responses [43]. Similar to the previous findings, our preliminary study also indicated that CopA3 inhibited the NO production in LPS-stimulated RAW264.7 cells ( Supplementary Figure 2A) [27]. Therefore, in our study, the effective inhibition of GNP-CK-CopA3 in LPS-induced production of NO and overexpression of mRNA and protein of pro-inflammatory cytokines was probably due to the combined role of both CopA3 and nanoparticles.…”

Section: Discussionsupporting

confidence: 90%

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Intracellular synthesis of gold nanoparticles by Gluconacetobacter liquefaciens for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages

Liu

Perumalsamy

Kang

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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Probiotic Gluconacetobacter strains are intestinal microbes with beneficial effects on human health. Recently, researchers have used these strains to biosynthesize metal and non-metal nanoparticles for treating various chronic diseases. Despite their importance in nanotechnology, gold nanoparticles (AuNPs) biosynthesized by Gluconacetobacter species have not been clearly identified for treating inflammation and inflammation-associated diseases. While ginsenoside CK has strong pharmaceutical activity, it also has strong cytotoxicity and hydrophobicity which is hurdle to make formulation. Peptide-nanoparticle hybrids are gaining increasing attention for their potential biomedical applications, including human inflammatory diseases. Herein, we developed peptide CopA3 surface conjugated and ginsenoside compound K (CK) loaded gold nanoparticles (GNP-CK-CopA3), which intracellularly synthesised by the probiotic Gluconacetobacter liquefaciens kh-1, to target lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The synthetic GNP-CK-CopA3 was characterised by various instrumental techniques. The results of our cellular uptake and MTT assays exhibited obvious drug intracellular delivery without significant cytotoxicity. In addition, pre-treatment with GNP-CK-CopA3 significantly ameliorated LPS-induced nitric oxide (NO) and reactive oxygen species (ROS) production and suppressed the mRNA and protein expression of pro-inflammatory cytokines in macrophages. Furthermore, GNP-CK-CopA3 efficiently inhibited the activation of the nuclear factor-jB (NF-jB) and mitogen-activating protein kinase (MAPK) signalling pathways. Taken together, our findings highlight the potential of using peptide-nanoparticle hybrids in the development of anti-inflammatory approaches and providing the experimental foundation for further application.

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Section: Discussionsupporting

confidence: 90%

“…It has been reported to exert antibacterial effects against various pathogenic bacteria [24] and selective anticancer on human gastric cancer cells [25]. CopA3 also ameliorated inflammatory responses in the gut [26] and lipopolysaccharide (LPS)induced macrophage activation [27].…”

mentioning

confidence: 99%

Intracellular synthesis of gold nanoparticles by Gluconacetobacter liquefaciens for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages

Liu

Perumalsamy

Kang

et al. 2020

Artificial Cells, Nanomedicine, and Biotechnology

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“…conspicillatum may defend itself against invading pathogens by developing strong antimicrobial compounds, among them HDP. Only a few HDP have been identified from a limited number of Coleopteran dung species, which include Copris tripartitus , with the CopA3 peptide [ 23 ] and Onthophagus taurus [ 24 ]. Therefore, the purpose of this study was to identify and functionally characterize new HDP from the O .…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of novel cecropins from the Oxysternon conspicillatum neotropic dung beetle

et al. 2017

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Dung beetles are exposed to a complex microbiological ecosystem during their life cycle. Characterization of novel host-defense peptides (HDP) is essential to understanding the host innate immune response in insects. It constitutes a promising alternative to look for new therapeutic agents against pathogenic microbes. We identified four new HDP, Oxysterlins 1, 2, 3, and 4 from the transcriptome of the Oxysternon conspicillatum dung beetle. These HDP display a highly conserved signal peptide and a mature peptide, characterized by an overall positive charge (cationic) (pI: 10.23–11.49), a hydrophobic ratio (ΦH: 35–41), and amphipathicity. Oxysterlins 1, 2, and 3 have a linear α-helix structure, whilst Oxysterlin 4 has a mixture of both α-helix and β-sheet structures without disulfide bonds through bioinformatics prediction and circular dichroism. Oxysterlins are part of the cecropin family group in an exclusive clade related to beetle cecropins. They have predominant antimicrobial activity against Gram-negative bacteria, including multidrug resistant strains (3.12–50 μg/mL) measured by plate microdilution. Their kinetics, in a time-killing curve showed concentration-dependent bactericidal activity. Furthermore, these HDP have low toxicity against human erythrocytes (62.5–500 μg/mL) and Vero cells (250–500 μg/mL). This article describes new HDP of the cecropin family from the Oxysternon conspicillatum dung beetle, with antimicrobial activity against multidrug resistant bacteria and low toxicity.

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“…Then, we prepared a dimeric form of CopA3 through a disulfide linkage and investigated its anti-inflammatory activities in LPS-induced macrophages. Coprisin and dimer CopA3 inhibited the expression of proinflammatory cytokines in LPS-activated Raw264.7 cells and/or mouse peritoneal macrophages [26,27]. Allomyrinasin and the aforementioned peptides are CAPs, which share common features such as a…”

Section: Allomyrinasin Reduces the Expression Of Proinflammatory Cytomentioning

confidence: 99%

Anti-Inflammatory Activity of Antimicrobial Peptide Allomyrinasin Derived from the Dynastid Beetle, Allomyrina dichotoma

Lee¹,

Seo²,

Lee³

et al. 2019

Journal of Microbiology and Biotechnology

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In a previous work, we performed de novo RNA sequencing of Allomyrina dichotoma using next generation sequencing and identified several antimicrobial peptide candidates based on transcriptome analysis. Among them, a cationic antimicrobial peptide, allomyrinasin, was selected bioinformatically based on its physicochemical properties. Here, we assessed the antimicrobial and anti-inflammatory activities of allomyrinasin against microorganisms and mouse macrophage Raw264.7 cells. Allomyrinasin showed antimicrobial activities against various microbes and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Furthermore, quantitative RT-PCR and ELISA revealed that allomyrinasin reduced cytokine expression levels in the Raw264.7 cells. We also identified inducible nitric oxide synthase, cyclooxygenase-2 expression, and PGE 2 production through western blot analysis and ELISA. We confirmed that allomyrinasin bound to bacterial cell membranes via a specific interaction with lipopolysaccharides. Taken together, these data indicate that allomyrinasin has antimicrobial and anti-inflammatory activities as exemplified in lipopolysaccharide-induced Raw264.7 cells. We have provided a potentially useful antimicrobial peptide candidate that has both antimicrobial and anti-inflammatory activities.

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The insect peptide CopA3 inhibits lipopolysaccharide‐induced macrophage activation

Cited by 13 publications

References 36 publications

Intracellular synthesis of gold nanoparticles by Gluconacetobacter liquefaciens for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages

Intracellular synthesis of gold nanoparticles by Gluconacetobacter liquefaciens for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages

Identification and characterization of novel cecropins from the Oxysternon conspicillatum neotropic dung beetle

Anti-Inflammatory Activity of Antimicrobial Peptide Allomyrinasin Derived from the Dynastid Beetle, Allomyrina dichotoma

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