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http://dx.doi.org/10.5352/JLS.2020.30.10.886

Anti-inflammatory Activity of Antimicrobial Peptide Papiliocin 3 Derived from the Swallowtail Butterfly, Papilio xuthus  

Shin, Yong Pyo (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Lee, Joon Ha (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Kim, In-Woo (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Seo, Minchul (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Kim, Mi-Ae (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Lee, Hwa Jeong (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Baek, Minhee (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Kim, Seong Hyun (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Hwang, Jae Sam (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration)
Publication Information
Journal of Life Science / v.30, no.10, 2020 , pp. 886-895 More about this Journal
Abstract
The development of novel peptide antibiotics with potent antimicrobial activity and anti-inflammatory activity is urgently needed. In a previous work, we performed an in-silico analysis of the Papilio xuthus transcriptome to identify putative antimicrobial peptides and identified several candidates. In this study, we investigated the antibacterial and anti-inflammatory activities of papiliocin 3, which was selected bioinformatically based on its physicochemical properties against bacteria and mouse macrophage Raw264.7 cells. Papiliocin 3 showed antibacterial activities against E. coli and S. aureus without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that papiliocin 3 reduced the expression levels of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, we examined whether papiliocin 3 could inhibit the expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) in LPS-induced Raw264.7 cells. We found that papiliocin 3 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling. We also confirmed that papiliocin 3 binds to bacterial cell membranes via a specific interaction with lipopolysaccharides. Collectively, these findings suggest that papiliocin 3 could be a promising molecule for development as a novel peptide antibiotic.
Keywords
Anti-inflammatory activity; antimicrobial activity; antimicrobial peptide; Papilio xuthus; RNA sequencing;
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1 Kell, D. B. and Pretorius, E. 2015. On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: the central roles of LPS and LPS-induced cell death. Integr. Biol. (Camb). 7, 1339-1377.   DOI
2 Lai, Y. and Gallo, R. L. 2009. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 30, 131-141.   DOI
3 Lasa, M., Mahtani, K. R., Finch, A., Brewer, G., Saklatvala, J. and Clark, A. R. 2000. Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade. Mol. Cell. Biol. 20, 4265-4274.   DOI
4 Lee, E. J., Shin, A. R. and Kim, Y. M. 2015. Anti-inflammatory activities of cecropin A and its mechanism of action. Arch. Insect Biochem. Physiol. 88, 31-44.   DOI
5 Leptihn, S., Har, J. Y., Wohland, T. and Ding, J. L. 2010. Correlation of charge, hydrophobicity, and structure with antimicrobial activity of S1 and MIRIAM peptides. Biochemistry 2, 9161-9170.
6 Locock, K. E. S., Michl, T. D., Valentin, J. D. P., Vasilev, K., Hayball, J. D., Qu, Y., Traven, A., Griesser, H. J., Meagher, L. and Haeussler, M. 2013. Guanylated polymethacrylates: a class of potent antimicrobial polymers with low hemolytic activity. Biomacromolecules 14, 4021-4031.   DOI
7 Lu, Y. C., Yeh, W. C. and Ohashi, P. S. 2008. LPS/TLR4 signal transduction pathway. Cytokine 42, 145-151.   DOI
8 Walkenhorst, W. F., Klein, J. W., Vo, P. and Wimley, W. C. 2013. pH Dependence of microbe sterilization by cationic antimicrobial peptides. Antimicrob. Agents Chemother. 57, 3312-3320.   DOI
9 Wang, J., Ma, K., Ruan, M., Wang, Y., Li, Y., Fu, Y. V., Song, Y., Sun, H. B. and Wang, J. 2018. A novel cecropin B-derived peptide with antibacterial and potential anti-inflammatory properties. PeerJ 6, e5369.   DOI
10 Yaakobi, K., Liebes-Peer, Y., Kushmaro, A. and Rapaport, H. 2013. Designed amphiphilic ${\beta}$-sheet peptides as templates for paraoxon adsorption and detection. Langmuir 29, 6840-6848.   DOI
11 Yeaman, M. R. and Yount, N. Y. 2003. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev. 55, 27-55.   DOI
12 Brogden, K. A. 2005. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3, 238-250.   DOI
13 Blondelle, S. E., Lohner, K. and Aguilar, M. 1999. Lipid-induced conformation and lipid-binding properties of cytolytic and antimicrobial peptides: determination and biological specificity. Biochim. Biophys. Acta. 15, 89-108.   DOI
14 Boman, H. G., Nilsson-Faye, I., Paul, K. and Rasmuson, Jr. T. 1974. Insect immunity. I. Characteristics of an inducible cell-free antibacterial reaction in hemolymph of Samia cynthia pupae. Infect. Immun. 10, 136-145.   DOI
15 Bowdish, D. M. E., Davidson, D. J., Scott, M. G. and Hancock, R. E. 2005. Immunomodulatory activities of small host defense peptides. Antimicrob. Agents Chemother. 49, 1727-1732.   DOI
16 Bulet, P., Stocklin, R. and Menin, L. 2004. Anti-microbial peptides: from invertebrates to vertebrates. Immunol. Rev. 198, 169-184.   DOI
17 Cruz, J., Ortiz, C., Guzman, F., Fernandez-Lafuente, R. and Torres, R. 2014. Antimicrobial peptides: promising compounds against pathogenic microorganisms. Curr. Med. Chem. 21, 2299-2321.   DOI
18 Dathe, M. and Wieprecht, T. 1999. Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. Biochim. Biophys. Acta. 15, 71-87.   DOI
19 Derache, C., Meudal, H., Aucagne, V., Mark, K. J., Cadene, M., Delmas, A. F., Lalmanach, A. C. and Celine, L. 2012. Initial insights into structure-activity relationships of avian defensins. J. Biol. Chem. 287, 7746-7755.   DOI
20 Ferrero-Miliani, L., Nielsen, O. H., Andersen, P. S. and Girardin, S. E. 2007. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin. Exp. Immunol. 147, 227-235.   DOI
21 Freudenthal, O., Quiles, F. and Francius G. 2017. Discrepancies between cyclic and linear antimicrobial peptide actions on the spectrochemical and nanomechanical fingerprints of a young biofilm. ACS. Omega 2, 5861-5872.   DOI
22 Giacometti, A., Cirioni, O., Ghiselli, R., Viticchi, C., Mocchegiani, F., Riva, A., Saba, V. and Scalise, G. 2001. Effect of mono-dose intraperitoneal cecropins in experimental septic shock. Crit. Care Med. 29, 1666-1669.   DOI
23 Guani-Guerra, E., Santos-Mendoza, T., Lugo-Reyes, S. O. and Teran, L. M. 2010. Antimicrobial peptides: general overview and clinical implications in human health and disease. Clin. Immunol. 135, 1-11.   DOI
24 Hancock, R. E., Nijnik, A. and Philpott, D. J. 2012. Modulating immunity as a therapy for bacterial infections. Nat. Rev. Microbiol. 10, 243-254.   DOI
25 Hancock, R. E. and Lehrer, R. 1998. Cationic peptides: a new source of antibiotics. Trends Biotechnol. 16, 82-88.   DOI
26 Hancock, R. E. and Sahl, H. G. 2006. Antimicrobial and hostdefense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 24, 1551-1557.   DOI
27 Harris S. G., Padilla, J., Koumas, L., Ray, D. and Phipps, R. P. 2002. Prostaglandins as modulators of immunity. Trends Immunol. 23, 144-150.   DOI
28 Heilborn, J. D., Nilsson, M. F., Kratz, G., Weber, G., Sorensen, O., Borregaard, N. and Stahle-Backdahl, M. 2003. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J. Invest. Dermatol. 120, 379-389.   DOI
29 Faye, I., Pye, A., Rasmuson, T., Boman, H. G. and Boman, I. A. 1975. Insect immunity. 11. Simultaneous induction of antibacterial activity and selection synthesis of some hemolymph proteins in diapausing pupae of Hyalophora cecropia and Samia cynthia. Infect. Immun. 12, 1426-1438.   DOI
30 Hollmann, A., Martinez, M., Maturana, P., Semorile, L. C. and Maffia, P. C. 2018. Antimicrobial peptides: Interaction with model and biological membranes and synergism with chemical antibiotics. Front. Chem. 6, 204.   DOI
31 Hultmark, D., Steiner, H., Rasmuson, T. and Boman, H. G. 1980. Insect immunity. Purification and properties of three inducible bactericidal proteins from hemolymph of immunized pupae of Hyalophora cecropia. Eur. J. Biochem. 106, 7-16.   DOI
32 Kim, J. K., Lee, E. J., Shin, S. Y., Jeong, K. W., Lee, J. Y., Bae, S. Y., Kim, S. H., Lee, J. Y., Kim, S. R., Lee, D. G., Hwang, J. S. and Kim, Y. M. 2011. Structure and function of papiliocin with antimicrobial and anti-inflammatory activities isolated from the swallowtail butterfly, Papilio xuthus. J. Biol. Chem. 286, 41296-41311.   DOI
33 Jozefiak, A. and Engberg, R. M. 2017. Insect proteins as a potential source of antimicrobial peptides in livestock production. A review. J. Anim. Feed Sci. 26, 87-99.   DOI
34 Kim, D. H. and Chung, J. Y. 2002. Akt: versatile mediator of cell survival and beyond. J. Biochem. Mol. Biol. 35, 106-115.
35 Kim, J. E., Jacob, B., Jang, M. H., Kwak, C. H., Lee, Y. J., Son, K., Lee, S. J., Jung, I. D., Jeong, M. S., Kwon, S. H. and Kim, Y. M. 2019. Development of a novel short 12-meric papiliocin-derived peptide that is effective against Gramnegative sepsis. Sci. Rep. 9, 3817.   DOI
36 Kim, S. R., Hong, M. Y., Park, S. W., Choi, K. H., Yun, E. Y., Goo, T. W., Kang, S. W., Suh, H. J., Kim, I. S. and Hwang, J. S. 2010. Characterization and cDNA cloning of a cecropin- like antimicrobial peptide, papiliocin, from the swallowtail butterfly, Papilio xuthus. Mol. Cells 29, 419-423.   DOI
37 McDonald, M., Mannion, M., Pike, D., Lewis, K., Flynn, A., Brannan, A. M., Browne, M. J., Jackman, D., Madera, L., Coombs, M. R. P., Hoskin, D. W., Rise, M. L. and Booth, V. 2015. Structure-function relationships in histidine-rich antimicrobial peptides from Atlantic cod. Biochim. Biophys. Acta. 1848, 1451-1461.   DOI
38 Nayduch, D., Lee, M. B. and Saski, C. A. 2014. Gene discovery and differential expression analysis of humoral immune response elements in female Culicoides sonorensis (Diptera: Ceratopogonidae). Parasit. Vectors 7, 388.   DOI
39 Norregaard, R., Kwon, T. H. and Frokiaer, J. 2015. Physiology and pathophysiology of cyclooxygenase-2 and prostaglandin E2 in the kidney. Res. Clin. Pract. 34, 194-200.
40 Niyonsaba, F., Ushio, H., Nakano, N., Ng, W., Sayama, K., Hashimoto, K., Nagaoka, I., Okumura, K. and Ogawa, H. 2007. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J. Invest. Dermatol. 127, 594-604.   DOI
41 Patocka, J., Nepovimova, E., Klimova, B., Wu, Q. and Kuca, K. 2019. Antimicrobial peptides: amphibian host defense peptides. Curr. Med. Chem. 26, 5924-5946.   DOI
42 Robertson, M. and Postlethwait, J. H. 1986. The humoral antibacterial response of drosophila adults. Dev. Comp. Immunol. 10, 167-179.   DOI
43 Steinberg, D. A. and Lehrer, R. I. 1997. Designer assays for antimicrobial peptides. disputing the "one-size-fits-all" theory. Methods Mol. Biol. 78, 169-186.
44 Vieira, C. S., Mattos, D. P., Waniek, P. J., Santangelo, J. M., Figueiredo, M. B., Gumiel, M., da Mota, F. F., Castro, D. P., Garcia, E. S. and Patricia, A. 2015. Rhodnius prolixus interaction with Trypanosoma rangeli: modulation of the immune system and microbiota population. Parasit. Vectors 8, 135.   DOI
45 Kim, S. Y., Park, S. W., Goo, T. W., Kang, S. W., Yun, E. Y. and Hwang, J. S. 2013. Recombinant antibacterial peptide papillocin 2 and its mass production method using the gene of papillocin 2 from Papilio xuthus. Korea patent 10-2013-0007783.
46 Kindrachuk, J. and Napper, S. 2010. Structure-activity relationships of multifunctional host defence peptides. Mini Rev. Med. Chem. 10, 596-614.   DOI