A Novel Cecropin-LL37 Hybrid Peptide Protects Mice Against EHEC Infection-Mediated Changes in Gut Microbiota, Intestinal Inflammation, and Impairment of Mucosal Barrier Functions
| Autor: | Maierhaba Aihemaiti, Lulu Zhang, Manyi Zhang, Baseer Ahmad, Rijun Zhang, Xubiao Wei, Junyong Wang, Dayong Si, Matthew D. Koci, Junhao Cheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Immunology Inflammation Peptide Gut flora Escherichia coli O157 Microbiology 03 medical and health sciences Mice hybrid peptide 0302 clinical medicine Cathelicidins medicine Escherichia coli Animals Immunology and Allergy Intestinal Mucosa Cytotoxicity O157:H7 mucosal barrier Escherichia coli Infections Original Research chemistry.chemical_classification biology Chemistry Cecropins biology.organism_classification Recombinant Proteins Gastrointestinal Microbiome Mice Inbred C57BL Intestinal Diseases 030104 developmental biology Cecropin Apoptosis Tumor necrosis factor alpha Female microflora medicine.symptom Signal transduction lcsh:RC581-607 enrofloxacin 030215 immunology Antimicrobial Cationic Peptides |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 11 (2020) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.01361 |
| Popis: | Intestinal inflammation can cause impaired epithelial barrier function and disrupt immune homeostasis, which increases the risks of developing many highly fatal diseases. Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes intestinal infections worldwide and is a major pathogen that induces intestinal inflammation. Various antibacterial peptides have been described as having the potential to suppress and treat pathogen-induced intestinal inflammation. Cecropin A (1–8)-LL37 (17–30) (C-L), a novel hybrid peptide designed in our laboratory that combines the active center of C with the core functional region of L, shows superior antibacterial properties and minimized cytotoxicity compared to its parental peptides. Herein, to examine whether C-L could inhibit pathogen-induced intestinal inflammation, we investigated the anti-inflammatory effects of C-L in EHEC O157:H7-infected mice. C-L treatment improved the microbiota composition and microbial community balance in mouse intestines. The hybrid peptide exhibited improved anti-inflammatory effects than did the antibiotic, enrofloxacin. Hybrid peptide treated infected mice demonstrated reduced clinical signs of inflammation, reduced weight loss, reduced expression of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ)], reduced apoptosis, and reduced markers of jejunal epithelial barrier function. The peptide also affected the MyD88–nuclear factor κB signaling pathway, thereby modulating inflammatory responses upon EHEC stimulation. Collectively, these findings suggest that the novel hybrid peptide C-L could be developed into a new anti-inflammatory agent for use in animals or humans. |
| Databáze: | OpenAIRE |
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