Antimicrobial peptides form part of the innate immune response and play a vital role in host defense against pathogens. Here we report a new antimicrobial peptide belonging to the cathelicidin family, cathelicidin-MH (cath-MH), from the skin of Microhyla heymonsivogt frog. Cath-MH has a single α-helical structure in membrane-mimetic environments and is antimicrobial against fungi and bacteria, especially Gram-negative bacteria. In contrast to other cathelicidins, cath-MH suppresses coagulation by affecting the enzymatic activities of tissue plasminogen activator, plasmin, β-tryptase, elastase, thrombin, and chymase. Cath-MH protects against lipopolysaccharide (LPS)- and cecal ligation and puncture-induced sepsis, effectively ameliorating multiorgan pathology and inflammatory cytokine through its antimicrobial, LPS-neutralizing, coagulation suppressing effects as well as suppression of MAPK signaling. Taken together, these data suggest that cath-MH is an attractive candidate therapeutic agent for the treatment of septic shock.
- MeSH
- antiinfekční látky chemie farmakologie MeSH
- fylogeneze MeSH
- kathelicidiny chemie farmakologie MeSH
- proteiny obojživelníků chemie farmakologie MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- sekvenční seřazení MeSH
- sepse farmakoterapie MeSH
- žáby * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The peptide LL-37, a component of the human innate immune system, represents a promising drug candidate. In particular, the development of low-cost production platform technology is a critical bottleneck in its use in medicine. In the present study, a viable approach for the LL-37 production in transgenic barley is developed. First, comparative analyses of the effects of different fused peptide epitope tags applicable for accumulation and purification on LL-37 production yield are performed using transient expression in tobacco leaves. Following the selection of the most yielding fusion peptide strategies, eight different constructs for the expression of codon optimized chimeric LL-37 genes in transgenic barley plants are created. The expression of individual constructs is driven either by an endosperm-specific promoter of the barley B1 hordein gene or by the maize ubiquitin promoter. The transgenes are stably integrated into the barley genome and inherited in the subsequent generation. All transgenic lines show normal phenotypes and are fertile. LL-37 accumulated in the barley seeds up to 0.55 mg per 1 kg of grain. The fused epitope tags are cleaved off by the use of enterokinase. Furthermore, in planta produced LL-37 including the fused versions is biologically active.
- MeSH
- geneticky modifikované rostliny genetika metabolismus MeSH
- ječmen (rod) genetika metabolismus MeSH
- kathelicidiny chemie genetika izolace a purifikace metabolismus MeSH
- lidé MeSH
- molekulární farmaření metody MeSH
- promotorové oblasti (genetika) genetika MeSH
- rekombinantní fúzní proteiny chemie genetika izolace a purifikace metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Tento přehled se zabývá obrannými (antimikrobiálními) peptidy. Je zřejmé, že antimikrobiální peptidy aktivně participují na vše ch úrovních imunitní obrany a mají klíčovou modulační úlohu v mechanismech vrozené imunity. Přispívají také k regulaci adaptivní imunity.
This review will discuss the host defense (antimicrobial) pept ides. There is emerging evidence that antimicrobial peptides acti vely participate in all stages of host immune defense and have key modulatory role in innate imunity and contribute to the regulation of host adapt ive imunity.
- MeSH
- aktivní imunita genetika imunologie účinky léků MeSH
- cytokiny chemie imunologie izolace a purifikace MeSH
- defensiny chemie imunologie izolace a purifikace MeSH
- imunita získaná od matky genetika imunologie účinky léků MeSH
- kathelicidiny chemie imunologie izolace a purifikace MeSH
- kationické antimikrobiální peptidy imunologie izolace a purifikace MeSH
- medicína založená na důkazech trendy MeSH
- Publikační typ
- kongresy MeSH
