Conformational Analysis of the Frog Skin Peptide, Plasticin-L1, and Its Effects on Production of Proinflammatory Cytokines by Macrophages

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• 作者：Mariano A. Scorciapino ; Giorgia Manzo ; Andrea C. Rinaldi ; Roberta Sanna ; Mariano Casu ; Jelena M. Pantic ; Miodrag L. Lukic ; J. Michael Conlon
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：October 15, 2013
• 年：2013
• 卷：52
• 期：41
• 页码：7231-7241
• 全文大小：558K
• 年卷期：v.52,no.41(October 15, 2013)
• ISSN：1520-4995

文摘

Plasticin-L1 (GLVNGLLSSVLGGGQGGGGLLGGIL) is a conformationally flexible glycine/leucine-rich peptide originally isolated from norepinephrine-stimulated skin secretions of the South-American Santa Fe frog Leptodactylus laticeps (Leptodactylidae). A nuclear magnetic resonance/molecular dynamics characterization of plasticin-L1 in the presence of dodecylphosphocholine (DPC) and DPC/sodium dodecylsulphate micelles as membrane-mimetic models showed that the peptide has affinity for both neutral and anionic membranes. The peptide adopts a stable helical conformation at the N-terminal region and a more disordered helix at the C-terminal region, separated by an unstructured loop wherein the highest number of glycines is localized. In both micelle environments, plasticin-L1 slowly inserts between the detergent head groups but always remains localized at the micelle/water interface. Plasticin-L1 lacks direct antimicrobial activity but stimulates cytokine production by macrophages. Incubation with plasticin-L1 (20 渭g/mL) significantly (P < 0.05) increased the production of the proinflammatory cytokines IL-1尾, IL-12, IL-23, and TNF-伪 from unstimulated peritoneal macrophages from both C57BL/6 and BALB/C mice. The peptide also increased IL-6 production by unstimulated (P < 0.01) and lipopolysaccharide-stimulated (P < 0.01) macrophages, whereas the effects on production of the anti-inflammatory cytokine IL-10 were not significant. These findings suggest that plasticin-L1 may play an immunomodulatory role in vivo by stimulating cytokine production from frog skin macrophages in response to microbial pathogens. This peptide may represent a template for the design of peptides with therapeutic applications as immunostimulatory agents.