WKYMVm ameliorates acute lung injury via neutrophil antimicrobial peptide derived STAT1/IRF1 pathway

Lee, Hanbyeol; Lee, Joo-Yeon; Park, Youngheon; Kim, Jae Ho; Eickelberg, Oliver; Yang, Se‐Ran

doi:10.1016/j.bbrc.2020.09.036

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…Due to the alarming increase in pathogen resistance to conventional antibiotics and threats to public health worldwide, the exploration of new drugs to treat infections caused by antimicrobial-resistant pathogens is urgently needed ( Alfei and Schito, 2020 ). Antimicrobial peptides are a class of small molecular peptides produced by the bodily innate immune system that can resist pathogenic infection and exhibit antibacterial, antiviral, anti-inflammatory, and immunoregulatory functions ( Faya et al, 2020 ; Lee et al, 2020 ). Antimicrobial peptides are currently considered as the best alternatives to antibiotics.…”

Section: Introductionmentioning

confidence: 99%

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

et al. 2021

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Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.

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Section: Introductionmentioning

confidence: 99%

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

et al. 2021

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“…Qin established a sepsis-induced acute lung injury model and found that the peptide LL-37 and its analogy sLL-37 attenuated the progression of sepsis-induced acute lung injury by inhibiting neutrophil infiltration and migration through the FAK, ERK, and P38 pathways [34]. In other studies, lipopolysaccharide (LPS)-and oleic acid (OA)-induced ALI animal models were established to evaluate the effect of peptides on ameliorating ALI [35][36][37]. In this study, we used peptide-induced mouse ALI to evaluate the in vivo cytotoxicity of the peptide.…”

Section: Discussionmentioning

confidence: 99%

A Rapid In Vivo Toxicity Assessment Method for Antimicrobial Peptides

Chi,

Peng,

Zhang

et al. 2024

Toxics

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Antimicrobial peptides (AMPs) represent a promising antibiotic alternative to overcome drug-resistant bacteria by inserting into the membrane of bacteria, resulting in cell lysis. However, therapeutic applications of AMPs have been hindered by their ability to lyse eukaryotic cells. GF-17 is a truncated peptide of LL-37, which has perfect amphipathicity and a higher hydrophobicity, resulting in higher haemolytic activity. However, there is no significant difference in the cytotoxicity against human lung epithelial cells between the GF-17 and LL-37 groups, indicating that there are significant differences in the sensitivity of different human cells to GF-17. In this study, LL-37 and GF-17 were administered to mouse lungs via intranasal inoculation. Blood routine examination results showed that LL-37 did not affect the red blood cells, platelet, white blood cells and neutrophil counts, but GF-17 decreased the white blood cells and neutrophil counts with the increasing concentration of peptides. GF-17-treated mice suffer a body weight loss of about 2.3 g on average in 24 h, indicating that GF-17 is highly toxic to mice. The total cell counts in the bronchoalveolar lavage fluid from GF-17-treated mice were 4.66-fold that in the untreated group, suggesting that GF-17 treatment leads to inflammation in the lungs of mice. Similarly, the histological results showed the infiltration of neutrophils in the lungs of GF-17-treated mice. The results suggest that the administration of GF-17 in the lungs of mice does not affect the red blood cells and platelet counts in the blood but promotes neutrophil infiltration in the lungs, leading to an inflammatory response. Therefore, we established a mouse acute lung injury model to preliminarily evaluate the in vivo toxicity of AMPs. For AMPs with a clinical application value, systematic research is still needed to evaluate their acute and long-term toxicity.

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“… 14 The half-maximal effective concentrations of WKYMVm for calcium mobilization through FPR2 and FPR3 were 75 pM and 3 nM, respectively. 15 The effects of WKYMVm on sepsis, 16 , 17 lung injury, 18 , 19 tumors, 20 , 21 bone defect repair, 22 insulin resistance, 23 neurodegenerative diseases 24 and other diseases have been frequently reported. For example, WKYMVm binds to FPR2 and activates the interleukin-6/gp130/signal transducer and activator of transcription 3 (IL-6/gp130/STAT3) signaling pathway to promote hepatocyte regeneration and alleviate liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

“…), which can react with bacterial substrates and kill bacteria. 19 , 42 , 43 Chemotherapy for cancer patients may lead to neutropenia, which makes patients prone to secondary infections. WKYMVm treatment has been reported to increase the production of ROS and bactericidal activity of neutrophils in patients receiving chemotherapy, but this effect needs to be confirmed by a large sample of clinical research.…”

Section: Introductionmentioning

confidence: 99%

WKYMVm Works by Targeting Immune Cells

Yang

Zhao²,

Jiang

et al. 2023

JIR

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WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met) is a synthetic hexapeptide identified as a potent agonist of FPRs. FPRs are widely expressed on the cell membrane of immune cells. Therefore, WKYMVm participates in the regulation of immune cells by activating FPRs, and plays a therapeutic role in infections, tumors, autoimmune diseases and so on. WKYMVm can promote the chemotactic migration, increase the bactericidal activity of neutrophils and monocytes. WKYMVm also regulates the number and polarization of macrophages, affects the maturation of DCs and the differentiation of T cells, and promotes the activation and chemotaxis of NK cells. These functions make WKYMVm a candidate drug for immunotherapy. In this paper, we summarize the regulatory effects and underlying mechanisms of WKYMVm on six immune cells (neutrophils, monocytes, macrophages, DCs, T cells and NK cells) to increase comprehensive understanding and promote further research on WKYMVm.

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WKYMVm ameliorates acute lung injury via neutrophil antimicrobial peptide derived STAT1/IRF1 pathway

Cited by 8 publications

References 19 publications

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

A Rapid In Vivo Toxicity Assessment Method for Antimicrobial Peptides

WKYMVm Works by Targeting Immune Cells

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