Immunomodulatory, insulinotropic, and cytotoxic activities of phylloseptins and plasticin-TR from the Trinidanian leaf frog Phyllomedusa trinitatis.
Animals
Anti-Inflammatory Agents
/ chemistry
Antimicrobial Cationic Peptides
/ chemistry
Anura
Cell Line
Cell Survival
/ drug effects
Cytotoxins
/ pharmacology
Eye Proteins
/ chemistry
Humans
Immunomodulation
/ drug effects
Insulin
/ metabolism
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins
/ chemistry
Rats
amphibian skin peptide
cytokine
cytotoxicity
insulin release
phylloseptin
plasticin
type 2 diabetes
Journal
Journal of peptide science : an official publication of the European Peptide Society
ISSN: 1099-1387
Titre abrégé: J Pept Sci
Pays: England
ID NLM: 9506309
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
24
11
2018
revised:
11
01
2019
accepted:
14
01
2019
pubmed:
9
2
2019
medline:
10
8
2019
entrez:
9
2
2019
Statut:
ppublish
Résumé
The aim of the study was to determine the in vitro immunomodulatory, cytotoxic, and insulin-releasing activities of seven phylloseptin-TR peptides and plasticin-TR, first isolated from the frog Phyllomedusa trinitatis. The most cationic peptides, phylloseptin-1.1TR and phylloseptin-3.1TR, showed greatest cytotoxic potency against A549, MDA-MB231, and HT-29 human tumor-derived cells and against mouse erythrocytes. Phylloseptin-4TR was the most hydrophobic and the most effective peptide at inhibiting production of the proinflammatory cytokines TNF-α and IL-1β by mouse peritoneal cells but was without effect on production of the antiinflammatory cytokine IL-10. Phylloseptin-2.1TR and phylloseptin-3.3TR were the most effective at stimulating the production of IL-10. The noncytotoxic peptide, plasticin-TR, inhibited production of TNF-α and IL-1β but was without effect on IL-10 production. The results of CD spectroscopy suggest that the different properties of plasticin-TR compared with the immunostimulatory activities of the previously characterized plasticin-L1 from Leptodactylus laticeps may arise from greater ability of plasticin-TR to oligomerize and adopt a stable helical conformation in a membrane-mimetic environment. All peptides stimulated release of insulin from BRIN-BD11 rat clonal β cells with phylloseptin-3.2TR being the most potent and effective and phylloseptin-2.1TR the least effective suggesting that insulinotropic potency correlates inversely with helicity. The study has provided insight into structure-activity relationships among the phylloseptins. The combination of immunomodulatory and insulinotropic activities together with low cytotoxicity suggests that phylloseptin-3.3TR and plasticin-TR may represent templates for the development of agents for use in antiinflammatory and type 2 diabetes therapies.
Substances chimiques
Anti-Inflammatory Agents
0
Antimicrobial Cationic Peptides
0
Cytotoxins
0
Eye Proteins
0
Insulin
0
Nerve Tissue Proteins
0
plasticin
148996-63-8
Types de publication
Journal Article
Langues
eng
Pagination
e3153Subventions
Organisme : Ministry of Education, Science and Technological Development, Serbia
ID : ON 175103
Organisme : Ministry of Education, Science and Technological Development, Serbia
ID : ON 175071
Organisme : Ministry of Education, Science and Technological Development, Serbia
ID : ON 175069
Organisme : University of the West Indies Campus Research and Publication Fund
ID : #26600-457118
Organisme : Labex Synorg
ID : ANR-11-LABX-0029
Organisme : Ulster University Strategic Funding
Organisme : Northern Ireland Department of Education and Learning (DEL)
Informations de copyright
© 2019 European Peptide Society and John Wiley & Sons, Ltd.