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Current IssueEditorial BoardOnline First ArticlesArchive
Current IssueEditorial BoardOnline First ArticlesArchive

volume 35 issue 4 (december 2014) : 299 - 306,   Doi: 10.5958/0976-0741.2014.00918.0

APPLICATIONS AND IMPLICATIONS OF MAMMALIAN ANTIMICROBIAL PEPTIDES- A REVIEW

S
Shahid Hussain
C
C.S. Mukhopadhyay*
J
J.S. Arora
1Post Graduate Institute of Veterinary Education and Research, Guru Angad Dev Veterinary and Animal University, Ludhiana-141 001, India
Cite article:- Hussain Shahid, Mukhopadhyay* C.S., Arora J.S. (2025). APPLICATIONS AND IMPLICATIONS OF MAMMALIAN ANTIMICROBIAL PEPTIDES- A REVIEW. Agricultural Reviews. 35(4): 299 - 306. doi: 10.5958/0976-0741.2014.00918.0.

ABSTRACT

Antimicrobial peptides are host defense peptides that are present in members of both Kingdoms Plantae vis-à-vis Animalia. These comprise of a number of structurally diverse peptides which are upto100 amino acid in length. These antimicrobial peptides are part of the inherent innate immune system of the host and are responsible for carrying out diverse activities ranging from killings the invading pathogens, modifying and regulating the immune system in executing these processes. In the immune system they have diverse functions such as acting as chemotaxis, modulation of inflammation, regulation of expression of inflammatory cytokines preventing hypersensitivity. Antimicrobial peptides are presently under trials for development of novel antibiotics which can be used for treatment of multidrug resistant pathogens. Currently different antimicrobial peptides are used as food preservatives and for prevention of microbes, like methicillin resistant S. aureus among others.

REFERENCES

  1. Bagella, L., Scocchi, M. and Zanetti, M (1995). cDNA sequences of three sheep myeloid cathelicidins. FEBS Lett., 376:225–228.
  2. Brandenburg, L.O., Jansen, S., Wruck, C.J., Lucius, R. and Pufe, T (2010). Antimicrobial peptide rCramp induced glial cell activation through p2y receptor signalling pathways. Mol. Immunol., 47:1905–1913.
  3. Buck, C. B., Day, P.M., Thompson, C.D., Lubkowski, J., Lu, D.W., Lowy, R. and Schiller, J.T (2006). Human alpha- defensins block papillomavirus infection. Proc. Natl. Acad. Sci. USA., 103:1516–1521.
  4. Castiglioni, B., Scocchi, M., Zanetti, M. and Ferretti, L (1996). Six antimicrobial peptide genes of the cathelicidin family map to bovine chromosome 22q24 by ûuorescence in situ hybridization. Cytogen. Cell Genet., 75:240–242.
  5. Cheigh, C.I. and Pyun, Y.R (2010). Nisin biosynthesis and its properties. Biotechnol. Lett. 27:1641–1648.
  6. Chen, X.F., Niyonsaba, H., Ushio, M., Hara, H., Yokoi, K.., Matsumoto, H., Saito, I., Nagaoka, S., Ikeda, and Okumura, K (2007). Antimicrobial peptides human beta-defensin (hbd)-3 and hbd-4 activate mast cells and increase skin vascular permeability. Eur. J. Immunol., 37:434–444.
  7. Coffelt, S.B., Waterman, R.S., Florez, L., Bentrup, K.H., Zwezdaryk, K.J., Tomchuck, S.L., Lamarca, H.L., Danka, E.S., Morris, C.A. and Scandurro, A.B (2008) Ovarian cancers overexpress the antimicrobial protein hCAP- 18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion. Int. J. Cancer., 122:1030-1039.
  8. Gallo, S.A., Wang, W., Rawat, S.S., Jung, G., Waring, A.J., Cole, A.M., Lu, H., Yan, X., Daly, N.L., Craik, D.J., Jiang, S., Lehrer, R.I. and Blumenthal, R (2006). Theta-defensins prevent hiv-1 env-mediated fusion by binding gp41 and blocking 6-helix bundle formation. J. Biol. Chem., 281(27):18787–18792.
  9. Ganguly, D., Chamilos, G., Lande, R., Gregorio, J., Meller, S., Facchinetti, V., Homey, B., Barrat, F.J., Zal, T. and Gilliet, M (2009) Self-rna-antimicrobial peptide complexes activate human dendritic cells through tlr7 and tlr8. J. Exp. Med., 206(9):1983–1994.
  10. Giuliani, A., Pirri, G., Bozzi, A., Giulio, A., Aschi, M. and Rinaldi, A.C (2008). Antimicrobial peptides: Natural templates for synthetic membrane-active compounds. Cell Mol Life Sci., 65(16):2450–2460.
  11. Haines, L.R., Thomas, J.M, Jackson, A.M, Eyford, B.A., Razavi, M., Watson, C.N., Gowen, B., Hancock, R.E. and Pearson, T.W (2009). Killing of trypanosomatid parasites by a modified bovine host defense peptide, bmap-18. PLoS Negl. Trop.Dis., 3(2)e373.
  12. John, H., Maronde, E., Forssmann, W.G., Meyer, M. and Adermann, K (2008). N-terminal acetylation protects glucagon- like peptide GLP-1-(7–34)-amide from DPP-IV-mediated degradation retaining cAMP- and insulin-releasing capacity. Eur J Med Res., 13:73–78
  13. Koczulla, R., Von Degenfeld, G., Kupatt, C., Krotz, F., Zahler, S., Gloe, T., Issbrucker, K., Unterberger, P., Zaiou, M. and Lebherz, C (2003). An angiogenic role for the human peptide antibiotic ll-37/hcap-18. J. Clin. Invest., 111(11):1665–1672.
  14. Kovacs-Nolan, J., Mapletoft, J.W., Latimer, L., Babiuk, L.A. and Hurk, S.Y (2009). CpG oligonucleotide, host defense peptide and polyphosphazene act synergistically, inducing long-lasting, balanced immune responses in cattle. Vaccine, 27(14):2048–2054.
  15. Lai, Y. and Gallo, R.L (2009). Amped up immunity: How antimicrobial peptides have multiple roles in immune defense. Trends Immunol., 30(3):131–141.
  16. Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.H., Homey B, Cao, W., Wang, Y.H., Su, B., Nestle, F.O., Zal, T., Mellman, I., Schro¨der, J.M., Liu, Y.J. and Gilliet, M (2007). Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature, 449:564-571.
  17. Larrick, J.W., Hiratam, M., Balint, R.F., Lee, J., Zhong, J. and Wright, S.C (1995). Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun., 63:1291–1297.
  18. Lee, H.S., Park, C.B., Kim, J.M., Jang, S.A., Park, I.Y., Kim, M.S., Cho, J.H. and Kim S.C (2008). Mechanism of anticancer activity of buforin iib, a histone h2a-derived peptide. Cancer Lett., 271(1):47–55.
  19. Lehrer, R.I. and Ganz, T (1999). Antimicrobial peptides in mammalian and insect host defence. Curr. Opin. Immunol., 11(1):23–27.
  20. Liang, J.F. and Kim, S.C (1999). Not only the nature of peptide but also the characteristics of cell membrane determine the antimicrobial mechanism of a peptide. J.Pep. Res., 53(5):518-522.Lina, M.C., Huib, C.F., Chenc, J.Y. and LeihWu, J (2013). Truncated antimicrobial peptides from marine organisms retain anticancer activity and antibacterial activity against multidrug-resistant Staphylococcus aureus. Peptides, 44:139–148.
  21. Lynn, M. A., Kindrachuk, J., Marr, A. K., Jenssen, H., Pante, N., Elliott, M. R., Napper, S., Hancock, R.E. and McMaster, W.R (2011). Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. PLoS Negl. Trop. Dis., 5(5):e1141
  22. McInturff, J.E., Wang, S.J., Machleidt, T., Lin, T.R., Oren, A., Hertz, C.J., Krutzik, S.R., Hart, S., Zeh, K., Anderson, D.H., Gallo. R.L., Modlin. R.L. and Kim, J (2005). Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against propionibacterium acnes. J. Invest. Dermatol., 125(2):256–263.
  23. Mihajlovic, M. and Lazaridis, T (2010). Antimicrobial peptides in toroidal and cylindrical pores. Biochim. Biophys. Acta., 1798(8):1485–1493
  24. Mukhopadhyay, C.S., Ravi Kumar, G.V.P.P.S. and Brah, G.S (2009). Gallinacin and Fowlicidin: Two Promising Antimicrobial Peptides in Chicken- A Review. Veterinary World, (6):297-300.
  25. Niyonsaba, F., Ushio, H., Nagaoka, I., Okumura, K. and Ogawa, H (2005). The human beta-defensins (-1, -2, -3,-4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J. Immunol., 175(3):1776–1784
  26. Ostergaard, C., Sandvang, D., Frimodt-Møller, N. and Kristensen, H.H (2009). High cerebrospinal fluid (csf) penetration and potent bactericidal activity in csf of nz2114, a novel plectasin variant, during experimental pneumococcal meningitis. Antimicrob. Agents Chemother., 53(4):1581–1585.
  27. Papo, N. and Shai Y (2004). Effect of drastic sequence alteration and d-amino acid incorporation on the membrane binding behavior of lytic peptides. Biochemistry, 43:6393–6403.
  28. Ritonja, A., Kopitar, M., Jerala, R. and Turk, V (1989). Primary structure of a new cysteine proteinase inhibitor from pig leucocytes. FEBS Lett., 255(2):211-214
  29. Rozek, A., Powers, J.P., Friedrich, C.L. and Hancock, R.E (2003). Structure-based design of an indolicidin peptide analogue with increased protease stability. Biochemistry, 42(48):14130-14138.
  30. Samad, A., Sultana, Y. and Aqil, M (2007). Liposomal drug delivery systems: an update review. Curr Drug. Deliv., 4:297–305.
  31. Sang, Y., Ortega, M.T., Blecha, F., Prakash, O. and Melgarejo, T (2005). Molecular cloning and characterization of three b-defensins from canine testis. Infection and Immunity, 73:2611–2620.
  32. Schrøder, H.D., Westergaard, M., Henningsen, J., Svendsen, M.L., Johansen, C., Jensen, U.B., Kratchmarova, I., Berge, R.K., Iversen, L., Bolund, L., Kragballe, K. and Kristiansen, K (2001). Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J. Invest. Dermatol., 116(5):702-712
  33. Scocchi, M., Bontempo, D., Boscolo, S., Tomasinsig, L., Giulotto, E. and Zanetti, M (1999). Novel cathelicidins in horse leukocytes. FEBS Lett., 57:459–464.
  34. Scott, M.G., Vreugdenhil, A.C., Buurman, W.A., Hancock, R.E. and Gold, M.R (2000). Cutting edge: Cationic antimicrobial peptides block the binding of lipopolysaccharide (lps) to lps binding protein. J. Immunol.,
  35. 164(2):549 553.
  36. Selsted, M.E., Szklarek, D., Ganz, T. and Lehrer, R.I. (1985) Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun., 49(1):202–206.
  37. Shamova, O., Brogden, K.A., Zhao, C., Nguyen, T., Kokryakov, V.N. and Lehrer, R.I (1999). Puriûcation and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes. Infect Immun., 67:4106–4111.
  38. Van der Does, A.M., Beekhuizen, H., Ravensbergen, B., Vos, T., Ottenhoff, T.H., van Dissel, J.T., Drijfhout, J.W., Hiemstra, P.S. and Nibbering, P.H (2010). LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature. J. Immunol., 185(3):1442–1449.
  39. Weber, G., Chamorro, C.I., Granath, F., Liljegren, A., Zreika, S., Saidak, Z., Sandstedt, B., Rotstein, S., Mentaverri, R., Sánchez, F., Pivarcsi, A. and Ståhle, M (2009). Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer. Breast Cancer Res., 11(1):R6.Wonga, J.H., Legowskab, A., Rolkab, K., Nga, T.Z., Huic, M., Choa, C.H., Lamd, W.W.L., Aud, S.W.N., Wangang, O., Gua and Wana, D.C.C (2011). Effects of cathelicidin and its fragments on three key enzymes of HIV-1. Peptides, 32:1117–1122
  40. Xiong, Y.Q., Hady, W.A., Deslandes, A., Rey, A., Fraisse, L., Kristensen, H.H., Yeaman, M.R. and Bayer, A.S (2010). Efficacy of nz2114, a novel plectasin-derived cationic antimicrobial peptide antibiotic, in experimental endocarditis due to methicillin-resistant staphylococcus aureus. Antimicrob. Agents Chemother., 55(11):5325–5330.
  41. Yan, H., Liu, Y., Tang, J., Mo, G., Song, Y., Yan, X., Wei, L. and Lai, L (2013). A Novel Antimicrobial Peptide from Skin Secretions of the Tree Frog Theloderma kwangsiensis. Zoolog. Sci., 30(9): 704-709
  42. Yang, D., Chen, Q., Chertov, O., Oppenheim, J.J (2000). Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. J. Leukoc. Biol., 68(1):9-14.
  43. Yang, D., Chertov, O. and Oppenheim, J.J (2001).Participation of mammalian defensins and cathelicidins in anti- microbial immunity: Receptors and activities of human defensins and cathelicidin (ll-37). J. Leuko. Biol., 69(5):691–697.
  44. Yang, D., de la Rosa, G., Tewary, P. and Oppenheim, J.J (2009). Alarmins Link Neutrophils and dendritic Cells. Trends Immunol., 30(11):531–537
  45. Yang, X., Wang, Y., Lee, W.H., Zhang, Y (2013). Antimicrobial peptides from the venom gland of the social wasp Vespa tropica. Toxicon, 74:151-7.
  46. Yeung, A.T., Gellatly, S.L and Hancock, R.E (2011). Multifunctional cationic host defense peptides and their clinical applications. Cell Mol Life Sci., 68(13):2161–2176.
  47. Zaiou, M., Nizet, V. and Gallo, R.L (2003). Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence. J Invest Dermato., 120(5):810-816.
  48. Zasloff M (1987). Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc. Natl. Acad. Sci., USA 84(15):5449-5453
  49. Zhang, J., Deng, J., Wang, Z., Che, C., Li, Y.F. and Yang, Q (2011). Modulatory effects of Lactobacillus salivarius on intestinal mucosal immunity of piglets. Current Microbiology., 62(5):1623-1631.
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    volume 35 issue 4 (december 2014) : 299 - 306,   Doi: 10.5958/0976-0741.2014.00918.0

    APPLICATIONS AND IMPLICATIONS OF MAMMALIAN ANTIMICROBIAL PEPTIDES- A REVIEW

    S
    Shahid Hussain
    C
    C.S. Mukhopadhyay*
    J
    J.S. Arora
    1Post Graduate Institute of Veterinary Education and Research, Guru Angad Dev Veterinary and Animal University, Ludhiana-141 001, India
    Cite article:- Hussain Shahid, Mukhopadhyay* C.S., Arora J.S. (2025). APPLICATIONS AND IMPLICATIONS OF MAMMALIAN ANTIMICROBIAL PEPTIDES- A REVIEW. Agricultural Reviews. 35(4): 299 - 306. doi: 10.5958/0976-0741.2014.00918.0.

    ABSTRACT

    Antimicrobial peptides are host defense peptides that are present in members of both Kingdoms Plantae vis-à-vis Animalia. These comprise of a number of structurally diverse peptides which are upto100 amino acid in length. These antimicrobial peptides are part of the inherent innate immune system of the host and are responsible for carrying out diverse activities ranging from killings the invading pathogens, modifying and regulating the immune system in executing these processes. In the immune system they have diverse functions such as acting as chemotaxis, modulation of inflammation, regulation of expression of inflammatory cytokines preventing hypersensitivity. Antimicrobial peptides are presently under trials for development of novel antibiotics which can be used for treatment of multidrug resistant pathogens. Currently different antimicrobial peptides are used as food preservatives and for prevention of microbes, like methicillin resistant S. aureus among others.

    REFERENCES

    1. Bagella, L., Scocchi, M. and Zanetti, M (1995). cDNA sequences of three sheep myeloid cathelicidins. FEBS Lett., 376:225–228.
    2. Brandenburg, L.O., Jansen, S., Wruck, C.J., Lucius, R. and Pufe, T (2010). Antimicrobial peptide rCramp induced glial cell activation through p2y receptor signalling pathways. Mol. Immunol., 47:1905–1913.
    3. Buck, C. B., Day, P.M., Thompson, C.D., Lubkowski, J., Lu, D.W., Lowy, R. and Schiller, J.T (2006). Human alpha- defensins block papillomavirus infection. Proc. Natl. Acad. Sci. USA., 103:1516–1521.
    4. Castiglioni, B., Scocchi, M., Zanetti, M. and Ferretti, L (1996). Six antimicrobial peptide genes of the cathelicidin family map to bovine chromosome 22q24 by ûuorescence in situ hybridization. Cytogen. Cell Genet., 75:240–242.
    5. Cheigh, C.I. and Pyun, Y.R (2010). Nisin biosynthesis and its properties. Biotechnol. Lett. 27:1641–1648.
    6. Chen, X.F., Niyonsaba, H., Ushio, M., Hara, H., Yokoi, K.., Matsumoto, H., Saito, I., Nagaoka, S., Ikeda, and Okumura, K (2007). Antimicrobial peptides human beta-defensin (hbd)-3 and hbd-4 activate mast cells and increase skin vascular permeability. Eur. J. Immunol., 37:434–444.
    7. Coffelt, S.B., Waterman, R.S., Florez, L., Bentrup, K.H., Zwezdaryk, K.J., Tomchuck, S.L., Lamarca, H.L., Danka, E.S., Morris, C.A. and Scandurro, A.B (2008) Ovarian cancers overexpress the antimicrobial protein hCAP- 18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion. Int. J. Cancer., 122:1030-1039.
    8. Gallo, S.A., Wang, W., Rawat, S.S., Jung, G., Waring, A.J., Cole, A.M., Lu, H., Yan, X., Daly, N.L., Craik, D.J., Jiang, S., Lehrer, R.I. and Blumenthal, R (2006). Theta-defensins prevent hiv-1 env-mediated fusion by binding gp41 and blocking 6-helix bundle formation. J. Biol. Chem., 281(27):18787–18792.
    9. Ganguly, D., Chamilos, G., Lande, R., Gregorio, J., Meller, S., Facchinetti, V., Homey, B., Barrat, F.J., Zal, T. and Gilliet, M (2009) Self-rna-antimicrobial peptide complexes activate human dendritic cells through tlr7 and tlr8. J. Exp. Med., 206(9):1983–1994.
    10. Giuliani, A., Pirri, G., Bozzi, A., Giulio, A., Aschi, M. and Rinaldi, A.C (2008). Antimicrobial peptides: Natural templates for synthetic membrane-active compounds. Cell Mol Life Sci., 65(16):2450–2460.
    11. Haines, L.R., Thomas, J.M, Jackson, A.M, Eyford, B.A., Razavi, M., Watson, C.N., Gowen, B., Hancock, R.E. and Pearson, T.W (2009). Killing of trypanosomatid parasites by a modified bovine host defense peptide, bmap-18. PLoS Negl. Trop.Dis., 3(2)e373.
    12. John, H., Maronde, E., Forssmann, W.G., Meyer, M. and Adermann, K (2008). N-terminal acetylation protects glucagon- like peptide GLP-1-(7–34)-amide from DPP-IV-mediated degradation retaining cAMP- and insulin-releasing capacity. Eur J Med Res., 13:73–78
    13. Koczulla, R., Von Degenfeld, G., Kupatt, C., Krotz, F., Zahler, S., Gloe, T., Issbrucker, K., Unterberger, P., Zaiou, M. and Lebherz, C (2003). An angiogenic role for the human peptide antibiotic ll-37/hcap-18. J. Clin. Invest., 111(11):1665–1672.
    14. Kovacs-Nolan, J., Mapletoft, J.W., Latimer, L., Babiuk, L.A. and Hurk, S.Y (2009). CpG oligonucleotide, host defense peptide and polyphosphazene act synergistically, inducing long-lasting, balanced immune responses in cattle. Vaccine, 27(14):2048–2054.
    15. Lai, Y. and Gallo, R.L (2009). Amped up immunity: How antimicrobial peptides have multiple roles in immune defense. Trends Immunol., 30(3):131–141.
    16. Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.H., Homey B, Cao, W., Wang, Y.H., Su, B., Nestle, F.O., Zal, T., Mellman, I., Schro¨der, J.M., Liu, Y.J. and Gilliet, M (2007). Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature, 449:564-571.
    17. Larrick, J.W., Hiratam, M., Balint, R.F., Lee, J., Zhong, J. and Wright, S.C (1995). Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun., 63:1291–1297.
    18. Lee, H.S., Park, C.B., Kim, J.M., Jang, S.A., Park, I.Y., Kim, M.S., Cho, J.H. and Kim S.C (2008). Mechanism of anticancer activity of buforin iib, a histone h2a-derived peptide. Cancer Lett., 271(1):47–55.
    19. Lehrer, R.I. and Ganz, T (1999). Antimicrobial peptides in mammalian and insect host defence. Curr. Opin. Immunol., 11(1):23–27.
    20. Liang, J.F. and Kim, S.C (1999). Not only the nature of peptide but also the characteristics of cell membrane determine the antimicrobial mechanism of a peptide. J.Pep. Res., 53(5):518-522.Lina, M.C., Huib, C.F., Chenc, J.Y. and LeihWu, J (2013). Truncated antimicrobial peptides from marine organisms retain anticancer activity and antibacterial activity against multidrug-resistant Staphylococcus aureus. Peptides, 44:139–148.
    21. Lynn, M. A., Kindrachuk, J., Marr, A. K., Jenssen, H., Pante, N., Elliott, M. R., Napper, S., Hancock, R.E. and McMaster, W.R (2011). Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: role of leishmanolysin in parasite survival. PLoS Negl. Trop. Dis., 5(5):e1141
    22. McInturff, J.E., Wang, S.J., Machleidt, T., Lin, T.R., Oren, A., Hertz, C.J., Krutzik, S.R., Hart, S., Zeh, K., Anderson, D.H., Gallo. R.L., Modlin. R.L. and Kim, J (2005). Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against propionibacterium acnes. J. Invest. Dermatol., 125(2):256–263.
    23. Mihajlovic, M. and Lazaridis, T (2010). Antimicrobial peptides in toroidal and cylindrical pores. Biochim. Biophys. Acta., 1798(8):1485–1493
    24. Mukhopadhyay, C.S., Ravi Kumar, G.V.P.P.S. and Brah, G.S (2009). Gallinacin and Fowlicidin: Two Promising Antimicrobial Peptides in Chicken- A Review. Veterinary World, (6):297-300.
    25. Niyonsaba, F., Ushio, H., Nagaoka, I., Okumura, K. and Ogawa, H (2005). The human beta-defensins (-1, -2, -3,-4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J. Immunol., 175(3):1776–1784
    26. Ostergaard, C., Sandvang, D., Frimodt-Møller, N. and Kristensen, H.H (2009). High cerebrospinal fluid (csf) penetration and potent bactericidal activity in csf of nz2114, a novel plectasin variant, during experimental pneumococcal meningitis. Antimicrob. Agents Chemother., 53(4):1581–1585.
    27. Papo, N. and Shai Y (2004). Effect of drastic sequence alteration and d-amino acid incorporation on the membrane binding behavior of lytic peptides. Biochemistry, 43:6393–6403.
    28. Ritonja, A., Kopitar, M., Jerala, R. and Turk, V (1989). Primary structure of a new cysteine proteinase inhibitor from pig leucocytes. FEBS Lett., 255(2):211-214
    29. Rozek, A., Powers, J.P., Friedrich, C.L. and Hancock, R.E (2003). Structure-based design of an indolicidin peptide analogue with increased protease stability. Biochemistry, 42(48):14130-14138.
    30. Samad, A., Sultana, Y. and Aqil, M (2007). Liposomal drug delivery systems: an update review. Curr Drug. Deliv., 4:297–305.
    31. Sang, Y., Ortega, M.T., Blecha, F., Prakash, O. and Melgarejo, T (2005). Molecular cloning and characterization of three b-defensins from canine testis. Infection and Immunity, 73:2611–2620.
    32. Schrøder, H.D., Westergaard, M., Henningsen, J., Svendsen, M.L., Johansen, C., Jensen, U.B., Kratchmarova, I., Berge, R.K., Iversen, L., Bolund, L., Kragballe, K. and Kristiansen, K (2001). Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J. Invest. Dermatol., 116(5):702-712
    33. Scocchi, M., Bontempo, D., Boscolo, S., Tomasinsig, L., Giulotto, E. and Zanetti, M (1999). Novel cathelicidins in horse leukocytes. FEBS Lett., 57:459–464.
    34. Scott, M.G., Vreugdenhil, A.C., Buurman, W.A., Hancock, R.E. and Gold, M.R (2000). Cutting edge: Cationic antimicrobial peptides block the binding of lipopolysaccharide (lps) to lps binding protein. J. Immunol.,
    35. 164(2):549 553.
    36. Selsted, M.E., Szklarek, D., Ganz, T. and Lehrer, R.I. (1985) Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun., 49(1):202–206.
    37. Shamova, O., Brogden, K.A., Zhao, C., Nguyen, T., Kokryakov, V.N. and Lehrer, R.I (1999). Puriûcation and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes. Infect Immun., 67:4106–4111.
    38. Van der Does, A.M., Beekhuizen, H., Ravensbergen, B., Vos, T., Ottenhoff, T.H., van Dissel, J.T., Drijfhout, J.W., Hiemstra, P.S. and Nibbering, P.H (2010). LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature. J. Immunol., 185(3):1442–1449.
    39. Weber, G., Chamorro, C.I., Granath, F., Liljegren, A., Zreika, S., Saidak, Z., Sandstedt, B., Rotstein, S., Mentaverri, R., Sánchez, F., Pivarcsi, A. and Ståhle, M (2009). Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer. Breast Cancer Res., 11(1):R6.Wonga, J.H., Legowskab, A., Rolkab, K., Nga, T.Z., Huic, M., Choa, C.H., Lamd, W.W.L., Aud, S.W.N., Wangang, O., Gua and Wana, D.C.C (2011). Effects of cathelicidin and its fragments on three key enzymes of HIV-1. Peptides, 32:1117–1122
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