Rhesus macaque u-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways

Journal of Leukocyte Biology

Volumn 98, Issue 6, 2015, Pages 1061-1070

  Tongaonkar, Prasad ^a   Trinh, Katie K ^a   Schaal, Justin B ^a   Tran, Dat ^a   Gulko, Percio S ^b   Ouellette, André J ^a   Selsted, Michael E ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Akt; I B ; Monocytes; THP 1; TLR

Indexed keywords

ANTIINFLAMMATORY AGENT; CYTOKINE; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 8; LIPOPOLYSACCHARIDE; MARIMASTAT; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; THETA DEFENSIN RTD 1; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ALPHA DEFENSIN; CYCLOPEPTIDE; DEFA1A3 PROTEIN, HUMAN; TOLL LIKE RECEPTOR;

ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOKINE RELEASE; DRUG EFFECT; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME INHIBITION; GENE EXPRESSION; HUMAN; HUMAN CELL; MACROPHAGE; MONOCYTE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RHESUS MONKEY; SIGNAL TRANSDUCTION; AGONISTS; CYTOLOGY; DRUG EFFECTS; FEMALE; GENE EXPRESSION REGULATION; IMMUNOLOGY; MALE; PHOSPHORYLATION; TUMOR CELL LINE;

ALPHA-DEFENSINS; CELL LINE, TUMOR; CYTOKINES; FEMALE; GENE EXPRESSION REGULATION; HUMANS; LIPOPOLYSACCHARIDES; MACROPHAGES; MALE; MAP KINASE SIGNALING SYSTEM; MONOCYTES; NF-KAPPA B; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PEPTIDES, CYCLIC; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; TOLL-LIKE RECEPTORS;

EID: 84948985602     PISSN: 07415400     EISSN: 19383673     Source Type: Journal    
DOI: 10.1189/jlb.3A0315-102R     Document Type: Article

References (57)

1. Ericksen, B., Wu, Z., Lu, W., Lehrer, R. I. (2005) Antibacterial activity and specificity of the six human a-defensins. Antimicrob. Agents Chemother. 49, 269-275.
2. Mambula, S. S., Simons, E. R., Hastey, R., Selsted, M. E., Levitz, S. M. (2000) Human neutrophil-mediated nonoxidative antifungal activity against Cryptococcus neoformans. Infect. Immun. 68, 6257-6264.
3. Newman, S. L., Gootee, L., Gabay, J. E., Selsted, M. E. (2000) Identification of constituents of human neutrophil azurophil granules that mediate fungistasis against Histoplasma capsulatum. Infect. Immun. 68, 5668-5672.
4. Aley, S. B., Zimmerman, M., Hetsko, M., Selsted, M. E., Gillin, F. D. (1994) Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides. Infect. Immun. 62, 5397-5403.
5. Daher, K. A., Selsted, M. E., Lehrer, R. I. (1986) Direct inactivation of viruses by human granulocyte defensins. J. Virol. 60, 1068-1074.
6. Bastian, A., Schäfer, H. (2001) Human a-defensin 1 (HNP-1) inhibits adenoviral infection in vitro. Regul. Pept. 101, 157-161.
7. Khine, A. A., Del Sorbo, L., Vaschetto, R., Voglis, S., Tullis, E., Slutsky, A. S., Downey, G. P., Zhang, H. (2006) Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Blood 107, 2936-2942.
8. Boniotto, M., Jordan, W. J., Eskdale, J., Tossi, A., Antcheva, N., Crovella, S., Connell, N. D., Gallagher, G. (2006) Human b-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob. Agents Chemother. 50, 1433-1441.
9. Ito, T., Tanabe, H., Ayabe, T., Ishikawa, C., Inaba, Y., Maemoto, A., Kono, T., Ashida, T., Fujiya, M., Kohgo, Y. (2012) Paneth cells regulate both chemotaxis of immature dendritic cells and cytokine production from epithelial cells. Tohoku J. Exp. Med. 227, 39-48.
10. Yin, L., Chino, T., Horst, O. V., Hacker, B. M., Clark, E. A., Dale, B. A., Chung, W. O. (2010) Differential and coordinated expression of defensins and cytokines by gingival epithelial cells and dendritic cells in response to oral bacteria. BMC Immunol. 11, 37.
11. Niyonsaba, F., Ushio, H., Nagaoka, I., Okumura, K., Ogawa, H. (2005) The human b-defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18secretion through p38 and ERK MAPK activation in primary human keratinocytes. J. Immunol. 175, 1776-1784.
12. Li, J., Zhu, H. Y., Beuerman, R. W. (2009) Stimulation of specific cytokines in human conjunctival epithelial cells by defensins HNP1, HBD2, and HBD 3. Invest. Ophthalmol. Vis. Sci. 50, 644-653.
13. Syeda, F., Liu, H. Y., Tullis, E., Liu, M., Slutsky, A. S., Zhang, H. (2008) Differential signaling mechanisms of HNP-induced IL-8 production in human lung epithelial cells and monocytes. J. Cell. Physiol. 214, 820-827.
14. Chertov O., Michiel, D. F., Xu, L., Wang, J. M., Tani, K., Murphy, W. J., Longo, D. L., Taub, D. D., Oppenheim, J. J. (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J. Biol. Chem. 271, 2935-2940.
15. Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schröder, J. M., Wang, J. M., Howard, O. M., Oppenheim, J. J. (1999) b-defensins: linking innate and adaptive immunity through dendritic and T cell CCR 6. Science 286, 525-528.
16. Grigat, J., Soruri, A., Forssmann, U., Riggert, J., Zwirner, J. (2007) Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human a-defensin family. J. Immunol. 179, 3958-3965.
17. Soruri, A., Grigat, J., Forssmann, U., Riggert, J., Zwirner, J. (2007) b-Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved. Eur. J. Immunol. 37, 2474-2486.
18. Selsted, M. E., Ouellette, A. J. (2005) Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 6, 551-557.
19. Lehrer, R. I., Cole, A. M., Selsted, M. E. (2012) u-Defensins: cyclic peptides with endless potential. J. Biol. Chem. 287, 27014-27019.
20. Tang, Y. Q., Yuan, J., Osapay, G., Osapay, K., Tran, D., Miller, C. J., Ouellette, A. J., Selsted, M. E. (1999) A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated a-defensins. Science 286, 498-502.
21. Leonova, L., Kokryakov, V. N., Aleshina, G., Hong, T., Nguyen, T., Zhao, C., Waring, A. J., Lehrer, R. I. (2001) Circular minidefensins and posttranslational generation of molecular diversity. J. Leukoc. Biol. 70, 461-464.
22. Garcia, A. E., Osapay, G., Tran, P. A., Yuan, J., Selsted, M. E. (2008) Isolation, synthesis, and antimicrobial activities of naturally occurring u-defensin isoforms from baboon leukocytes. Infect. Immun. 76, 5883-5891.
23. Tongaonkar, P., Tran, P., Roberts, K., Schaal, J., Osapay, G., Tran, D., Ouellette, A. J., Selsted, M. E. (2011) Rhesus macaque u-defensin isoforms: expression, antimicrobial activities, and demonstration of a prominent role in neutrophil granule microbicidal activities. J. Leukoc. Biol. 89, 283-290.
24. Nguyen, T. X., Cole, A. M., Lehrer, R. I. (2003) Evolution of primate u-defensins: a serpentine path to a sweet tooth. Peptides 24, 1647-1654.
25. Yang, D., Biragyn, A., Hoover, D. M., Lubkowski, J., Oppenheim, J. J. (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosinophilderived neurotoxin in host defense. Annu. Rev. Immunol. 22, 181-215.
26. Schaal, J. B., Tran, D., Tran, P., Ö sapay, G., Trinh, K., Roberts, K. D., Brasky, K.M., Tongaonkar, P., Ouellette, A. J., Selsted, M. E. (2012) Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis. PLoS One 7, e51337.
27. Wohlford-Lenane, C. L., Meyerholz, D. K., Perlman, S., Zhou, H., Tran, D., Selsted, M. E., McCray, P. B., Jr. (2009) Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease. J. Virol. 83, 11385-11390.
28. Ganz, T., Selsted, M. E., Szklarek, D., Harwig, S. S., Daher, K., Bainton, D. F., Lehrer, R. I. (1985) Defensins: natural peptide antibiotics of human neutrophils. J. Clin. Invest. 76, 1427-1435.
29. Tongaonkar, P., Golji, A. E., Tran, P., Ouellette, A. J., Selsted, M. E. (2012) High fidelity processing and activation of the human a-defensin HNP1 precursor by neutrophil elastase and proteinase 3. PLoS One 7, e32469.
30. Lee, J., Mira-Arbibe, L., Ulevitch, R. J. (2000) TAK1 regulates multiple protein kinase cascades activated by bacterial lipopolysaccharide. J. Leukoc. Biol. 68, 909-915.
31. Guha, M., Mackman, N. (2002) The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J. Biol. Chem. 277, 32124-32132.
32. Yasin, B., Wang, W., Pang, M., Cheshenko, N., Hong, T., Waring, A. J., Herold, B. C., Wagar, E. A., Lehrer, R. I. (2004) Theta defensins protect cells from infection by herpes simplex virus by inhibiting viral adhesion and entry. J. Virol. 78, 5147-5156.
33. Cole, A. M., Hong, T., Boo, L. M., Nguyen, T., Zhao, C., Bristol, G., Zack, J. A., Waring, A. J., Yang, O. O., Lehrer, R. I. (2002) Retrocyclin: a primate peptide that protects cells from infection by T-and M-tropic strains of HIV-1. Proc. Natl. Acad. Sci. USA 99, 1813-1818.
34. Seidel, A., Ye, Y., de Armas, L. R., Soto, M., Yarosh, W., Marcsisin, R. A., Tran, D., Selsted, M. E., Camerini, D. (2010) Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms. PLoS One 5, e9737.
35. Doss, M., Ruchala, P., Tecle, T., Gantz, D., Verma, A., Hartshorn, A., Crouch, E. C., Luong, H., Micewicz, E. D., Lehrer, R. I., Hartshorn, K. L. (2012) Hapivirins and diprovirins: novel u-defensin analogs with potent activity against influenza A virus. J. Immunol. 188, 2759-2768.
36. Welkos, S., Cote, C. K., Hahn, U., Shastak, O., Jedermann, J., Bozue, J., Jung, G., Ruchala, P., Pratikhya, P., Tang, T., Lehrer, R. I., Beyer, W. (2011) Humanized u-defensins (retrocyclins) enhance macrophage performance and protect mice from experimental anthrax infections. Antimicrob. Agents Chemother. 55, 4238-4250.
37. Hayden, M. S., Ghosh, S. (2011) NF-kB in immunobiology. Cell Res. 21, 223-244.
38. Newton, K., Dixit, V. M. (2012) Signaling in innate immunity and inflammation. Cold Spring Harb. Perspect. Biol. 4, pii:a006059.
39. Mahtani, K. R., Brook, M., Dean, J. L., Sully, G., Saklatvala, J., Clark, A. R. (2001) Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor a mRNA stability. Mol. Cell. Biol. 21, 6461-6469.
40. Rutault, K., Hazzalin, C. A., Mahadevan, L. C. (2001) Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-a (TNF-a) mRNA induction. Evidence for selective destabilization of TNF-a transcripts. J. Biol. Chem. 276, 6666-6674.
41. Winzen, R., Kracht, M., Ritter, B., Wilhelm, A., Chen, C. Y., Shyu, A. B., Müller, M., Gaestel, M., Resch, K., Holtmann, H. (1999) The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. 18, 4969-4980.
42. Wang, S. W., Pawlowski, J., Wathen, S. T., Kinney, S. D., Lichenstein, H. S., Manthey, C. L. (1999) Cytokine mRNA decay is accelerated by an inhibitor of p38-mitogen-activated protein kinase. Inflamm. Res. 48, 533-538.
43. Holtmann, H., Winzen, R., Holland, P., Eickemeier, S., Hoffmann, E., Wallach, D., Malinin, N. L., Cooper, J. A., Resch, K., Kracht, M. (1999) Induction of interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine-or stressactivated signal transduction pathways. Mol. Cell. Biol. 19, 6742-6753.
44. Frevel, M. A., Bakheet, T., Silva, A. M., Hissong, J. G., Khabar, K. S., Williams, B. R. (2003) p38 Mitogen-activated protein kinase-dependent and-independent signaling of mRNA stability of AU-rich elementcontaining transcripts. Mol. Cell. Biol. 23, 425-436.
45. Dumitru, C. D., Ceci, J. D., Tsatsanis, C., Kontoyiannis, D., Stamatakis, K., Lin, J. H., Patriotis, C., Jenkins, N. A., Copeland, N. G., Kollias, G., Tsichlis, P. N. (2000) TNF-a induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 103, 1071-1083.
46. Karin, M. (2005) Inflammation-activated protein kinases as targets for drug development. Proc. Am. Thorac. Soc. 2, 386-390, discussion 394-395.
47. Park, Y. C., Lee, C. H., Kang, H. S., Chung, H. T., Kim, H. D. (1997) Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, enhances LPS-induced NO production from murine peritoneal macrophages. Biochem. Biophys. Res. Commun. 240, 692-696.
48. Fukao, T., Koyasu, S. (2003) PI3K and negative regulation of TLR signaling. Trends Immunol. 24, 358-363.
49. Zong, Y., Sun, L., Liu, B., Deng, Y. S., Zhan, D., Chen, Y. L., He, Y., Liu, J., Zhang, Z. J., Sun, J., Lu, D. (2012) Resveratrol inhibits LPS-induced MAPKs activation via activation of the phosphatidylinositol 3-kinase pathway in murine RAW 264.7 macrophage cells. PLoS One 7, e44107.
50. Schabbauer, G., Tencati, M., Pedersen, B., Pawlinski, R., Mackman, N. (2004) PI3K-Akt pathway suppresses coagulation and inflammation in endotoxemic mice. Arterioscler. Thromb. Vasc. Biol. 24, 1963-1969.
51. Williams, D. L., Li, C., Ha, T., Ozment-Skelton, T., Kalbfleisch, J. H., Preiszner, J., Brooks, L., Breuel, K., Schweitzer, J. B. (2004) Modulation of the phosphoinositide 3-kinase pathway alters innate resistance to polymicrobial sepsis. J. Immunol. 172, 449-456.
52. Röhrl, J., Yang, D., Oppenheim, J. J., Hehlgans, T. (2010) Human b-defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR 2. J. Immunol. 184, 6688-6694.
53. Semple, F., MacPherson, H., Webb, S., Cox, S. L., Mallin, L. J., Tyrrell, C., Grimes, G. R., Semple, C. A., Nix, M. A., Millhauser, G. L., Dorin, J. R. (2011) Human b-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF. Eur. J. Immunol. 41, 3291-3300.
54. Semple, F., Webb, S., Li, H.N., Patel, H. B., Perretti, M., Jackson, I. J., Gray, M., Davidson, D. J., Dorin, J. R. (2010) Human b-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur. J. Immunol. 40, 1073-1078.
55. Zheng, Y., Niyonsaba, F., Ushio, H., Nagaoka, I., Ikeda, S., Okumura, K., Ogawa, H. (2007) Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br. J. Dermatol. 157, 1124-1131.
56. Kahlenberg, J. M., Kaplan, M. J. (2013) Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J. Immunol. 191, 4895-4901.
57. Mookherjee, N., Brown, K. L., Bowdish, D. M., Doria, S., Falsafi, R., Hokamp, K., Roche, F. M., Mu, R., Doho, G. H., Pistolic, J., Powers, J. P., Bryan, J., Brinkman, F. S., Hancock, R. E. (2006) Modulation of the TLRmediated inflammatory response by the endogenous human host defense peptide LL-37. J. Immunol. 176, 2455-2464.