TY - JOUR
T1 - Host-defense peptides AC12, DK16 and RC11 with immunomodulatory activity isolated from Hypsiboas raniceps skin secretion
AU - Popov, Cláudia S.F.C.
AU - Magalhães, Beatriz Simas
AU - Goodfellow, Brian James
AU - Bocca, Anamélia Lorenzetti
AU - Pereira, David M.
AU - Andrade, Paula B.
AU - Valentão, Patrícia
AU - Pereira, Pedro José Barbosa
AU - Rodrigues, João Eduardo
AU - de Holanda Veloso, Paulo H.
AU - Rezende, Taia M.B.
N1 - Funding Information:
This study was supported by CAPES, CNPq, FAPDF and Universidade Católica de Brasília. We thank i3S, Faculdade de Farmácia da Universidade do Porto, Departamento de Química da Universidade de Aveiro and Universidade de Brasília for collaboration. This work received financial support from National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência) through project UID/QUI/50006/2013, co-financed by the European Union (FEDER under the Partnership Agreement PT2020). This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).
Funding Information:
This study was supported by CAPES, CNPq, FAPDF and Universidade Católica de Brasília . We thank i3S, Faculdade de Farmácia da Universidade do Porto, Departamento de Química da Universidade de Aveiro and Universidade de Brasília for collaboration. This work received financial support from National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência) through project UID/QUI/50006/2013, co-financed by the European Union (FEDER under the Partnership Agreement PT2020) . This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC ).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/3
Y1 - 2019/3
N2 - Inflammation is a natural defense mechanism of the immune system; however, when unregulated, it can lead to chronic illness. Glucocorticoids are the most commonly used agents to effectively treat inflammatory conditions, including autoimmune diseases, however these substances can trigger a number of side effects. Thus, viable alternatives to the use of these drugs would be advantageous. In this study, we have analyzed the anti-inflammatory profile of three synthetic peptides first identified in skin secretion of the tree frog Hypsiboas raniceps. Structural characterization was performed using NMR spectroscopy and Mass Spectrometry, and the peptides were tested in vitro in RAW 264.7 cells and in vivo in Balb/c mice for their functional properties. The samples did not show a significant antimicrobial profile. NMR spectroscopy indicated that AC12 (ACFLTRLGTYVC) has a disulfide bond between C2 and C11 and a β-sheet-turn-β-sheet conformation in aqueous solution. This peptide showed no cytotoxic effect in mammalian cells and it was the most effective in reducing anti-inflammatory markers, such as NO, TNF-α and IL-12. Peptide DK16 (DKERPICSNTFRGRKC) demonstrated anti-inflammatory properties in vitro, while RC11 (RCFRRRGKLTC) significantly altered the cell viability in RAW 264.7 but was shown to be safe in Balb/c erythrocytes. Our results indicate that, of the three peptides studied, AC12 is the most efficient in reducing anti-inflammatory markers, and it could be a potential agent for the treatment of inflammatory diseases.
AB - Inflammation is a natural defense mechanism of the immune system; however, when unregulated, it can lead to chronic illness. Glucocorticoids are the most commonly used agents to effectively treat inflammatory conditions, including autoimmune diseases, however these substances can trigger a number of side effects. Thus, viable alternatives to the use of these drugs would be advantageous. In this study, we have analyzed the anti-inflammatory profile of three synthetic peptides first identified in skin secretion of the tree frog Hypsiboas raniceps. Structural characterization was performed using NMR spectroscopy and Mass Spectrometry, and the peptides were tested in vitro in RAW 264.7 cells and in vivo in Balb/c mice for their functional properties. The samples did not show a significant antimicrobial profile. NMR spectroscopy indicated that AC12 (ACFLTRLGTYVC) has a disulfide bond between C2 and C11 and a β-sheet-turn-β-sheet conformation in aqueous solution. This peptide showed no cytotoxic effect in mammalian cells and it was the most effective in reducing anti-inflammatory markers, such as NO, TNF-α and IL-12. Peptide DK16 (DKERPICSNTFRGRKC) demonstrated anti-inflammatory properties in vitro, while RC11 (RCFRRRGKLTC) significantly altered the cell viability in RAW 264.7 but was shown to be safe in Balb/c erythrocytes. Our results indicate that, of the three peptides studied, AC12 is the most efficient in reducing anti-inflammatory markers, and it could be a potential agent for the treatment of inflammatory diseases.
KW - Anti-inflammatory
KW - Anura
KW - Immunomodulatory
KW - NMR
KW - Peptide
UR - http://www.scopus.com/inward/record.url?scp=85059815889&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2018.12.007
DO - 10.1016/j.peptides.2018.12.007
M3 - Article
C2 - 30610885
AN - SCOPUS:85059815889
SN - 0196-9781
VL - 113
SP - 11
EP - 21
JO - Peptides
JF - Peptides
ER -
