An antagonist of human protease activated receptor-2 attenuates PAR2 signaling, macrophage activation, mast cell degranulation, and collagen-induced arthritis in rats

FASEB Journal

Volumn 26, Issue 7, 2012, Pages 2877-2887

  Lohman, Rink Jan ^a   Cotterell, Adam J ^a   Barry, Grant D ^a   Liu, Ligong ^a   Suen, Jacky Y ^a   Vesey, David A ^a   Fairlie, David P ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

tryptase; Joint inflammation

Indexed keywords

ANTIINFLAMMATORY AGENT; CALCIUM ION; CARRAGEENAN; ENMD 1068; GB 88; PROTEINASE ACTIVATED RECEPTOR 2; PROTEINASE INHIBITOR; TRYPTASE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CALCIUM CELL LEVEL; CELL INFILTRATION; CELL SURFACE; CHRONIC ARTHRITIS; COLLAGEN DEGRADATION; CONTROLLED STUDY; FEMALE; FLUORESCENCE ANALYSIS; HISTOPATHOLOGY; HYPERPLASIA; IC 50; IN VITRO STUDY; MACROPHAGE ACTIVATION; MALE; MAST CELL DEGRANULATION; NONHUMAN; PANNUS; PAW EDEMA; PRIORITY JOURNAL; PROTEIN DEGRADATION; RAT; WISTAR RAT;

ADMINISTRATION, ORAL; ANIMALS; ARTHRITIS, EXPERIMENTAL; BIOLOGICAL AVAILABILITY; CELL DEGRANULATION; DIPEPTIDES; FEMALE; HUMANS; ISOXAZOLES; MACROPHAGE ACTIVATION; MALE; MAST CELLS; MODELS, BIOLOGICAL; OLIGOPEPTIDES; RATS; RATS, WISTAR; RECEPTOR, PAR-2; SIGNAL TRANSDUCTION;

RATTUS; RATTUS NORVEGICUS;

EID: 84863224546     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.11-201004     Document Type: Article

References (61)

1. Pejler, G., Ronnberg, E., Waern, I., and Wernersson, S. (2010) Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 115, 4981-4990
2. Teronen, O., Hietanen, J., Lindqvist, C., Salo, T., Sorsa, T., Eklund, K. K., Sommerhoff, C. P., Ylipaavalniemi, P., and Konttinen, Y. T. (1996) Mast cell-derived tryptase in odontogenic cysts. J. Oral Pathol. Med. 25, 376-381 (Pubitemid 26369405)
3. Morris, R., Winyard, P. G., Blake, D. R., and Morris, C. J. (1994) Thrombin in inflammation and healing: relevance to rheumatoid arthritis. Ann. Rheum. Dis. 53, 72-79 (Pubitemid 24067415)
4. Moore, C. S., and Crocker, S. J. (2012) An alternate perspective on the roles of TIMPs and MMPs in pathology. Am. J. Pathol. 180, 12-16
5. Cudic, M., and Fields, G. B. (2009) Extracellular proteases as targets for drug development. Curr. Protein Pept. Sci. 10, 297-307
6. Baugh, M., Black, D., Westwood, P., Kinghorn, E., McGregor, K., Bruin, J., Hamilton, W., Dempster, M., Claxton, C., Cai, J., Bennett, J., Long, C., McKinnon, H., Vink, P., den Hoed, L., Gorecka, M., Vora, K., Grant, E., Percival, M. D., Boots, A. M., and van Lierop, M. J. (2011) Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity. J. Autoimmun. 36, 201-209
7. Ino, Y., Sato, T., Koshiyama, Y., Suzuki, K., Oda, M., and Iwaki, M. (1987) Effects of FUT-175, a novel synthetic protease inhibitor, on the development of adjuvant arthritis in rats and some biological reactions dependent on complement activation. Gen. Pharmacol. 18, 513-516 (Pubitemid 17095124)
8. Isozaki, Y., Yoshida, N., Kuroda, M., Handa, O., Takagi, T., Kokura, S., Ichikawa, H., Naito, Y., Okanoue, T., and Yoshikawa, T. (2006) Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on experimental colitis. Scand. J. Gastroenterol. 41, 944-953 (Pubitemid 43995470)
9. Cho, E. Y., Choi, S. C., Lee, S. H., Ahn, J. Y., Im, L. R., Kim, J. H., Xin, M., Kwon, S. U., Kim, D. K., and Lee, Y. M. (2011) Nafamostat mesilate attenuates colonic inflammation and mast cell infiltration in the experimental colitis. Int. Immunopharmacol. 11, 412-417
10. Huang, T. Y., Chu, H. C., Lin, Y. L., Lin, C. K., Hsieh, T. Y., Chang, W. K., Chao, Y. C., and Liao, C. L. (2009) Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases. Toxicol. Appl. Pharmacol. 237, 69-82
11. Cattaruzza, F., Lyo, V., Jones, E., Pham, D., Hawkins, J., Kirkwood, K., Valdez-Morales, E., Ibeakanma, C., Vanner, S. J., Bogyo, M., and Bunnett, N. W. (2011) Cathepsin S is activated during colitis and causes visceral hyperalgesia by a PAR(2)-dependent mechanism in mice. Gastroenterology 141, 1864-1874
12. Macfarlane, S. R., Seatter, M. J., Kanke, T., Hunter, G. D., and Plevin, R. (2001) Proteinase-activated receptors. Pharmacol. Rev. 53, 245-282 (Pubitemid 32476117)
13. Adams, M. N., Ramachandran, R., Yau, M. K., Suen, J. Y., Fairlie, D. P., Hollenberg, M. D., and Hooper, J. D. (2011) Structure, function and pathophysiology of protease activated receptors. Pharmacol. Ther. 130, 248-282
14. Lohman, R. J., O'Brien, T. J., and Cocks, T. M. (2008) Protease-activated receptor-2 regulates trypsin expression in the brain and protects against seizures and epileptogenesis. Neurobiol. Dis. 30, 84-93
15. Cocks, T. M., and Moffatt, J. D. (2000) Protease-activated receptors: sentries for inflammation? Trends Pharmacol. Sci. 21, 103-108 (Pubitemid 30114325)
16. Kawabata, A., Matsunami, M., and Sekiguchi, F. (2008) Gastrointestinal roles for proteinase-activated receptors in health and disease. Br. J. Pharmacol. 153(Suppl. 1), S230-S240 (Pubitemid 351340981)
17. Sharma, A., Tao, X., Gopal, A., Ligon, B., Andrade-Gordon, P., Steer, M. L., and Perides, G. (2005) Protection against acute pancreatitis by activation of protease-activated receptor-2. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G388-G395 (Pubitemid 40129591)
18. Singh, V. P., Bhagat, L., Navina, S., Sharif, R., Dawra, R., and Saluja, A. K. (2006) PAR-2 protects against pancreatitis by stimulating exocrine secretion. Gut 56, 958-964
19. Amiable, N., Tat, S. K., Lajeunesse, D., Duval, N., Pelletier, J. P., Martel-Pelletier, J., and Boileau, C. (2009) Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts. Bone 44, 1143-1150
20. Boileau, C., Amiable, N., Martel-Pelletier, J., Fahmi, H., Duval, N., and Pelletier, J. P. (2007) Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study. Arthritis Res. Ther. 9, R121
21. Sawamukai, N., Yukawa, S., Saito, K., Nakayamada, S., Kambayashi, T., and Tanaka, Y. (2010) Mast cell-derived tryptase inhibits apoptosis of human rheumatoid synovial fibroblasts via rho-mediated signaling. Arthritis Rheum. 62, 952-959
22. Xue, M., Chan, Y. K., Shen, K., Dervish, S., March, L., Sambrook, P. N., and Jackson, C. J. (2012) Protease-activated receptor 2, rather than protease-activated receptor 1, contributes to the aggressive properties of synovial fibroblasts in rheumatoid arthritis. Arthritis Rheum. 64, 88-98
23. Busso, N., Frasnelli, M., Feifel, R., Cenni, B., Steinhoff, M., Hamilton, J., and So, A. (2007) Evaluation of protease-activated receptor 2 in murine models of arthritis. Arthritis Rheum. 56, 101-107 (Pubitemid 46106182)
24. Ferrell, W. R., Lockhart, J. C., Kelso, E. B., Dunning, L., Plevin, R., Meek, S. E., Smith, A. J., Hunter, G. D., McLean, J. S., McGarry, F., Ramage, R., Jiang, L., Kanke, T., and Kawagoe, J. (2003) Essential role for proteinase-activated receptor-2 in arthritis. J. Clin. Invest. 111, 35-41 (Pubitemid 36134846)
25. Kelso, E. B., Ferrell, W. R., Lockhart, J. C., Elias-Jones, I., Hembrough, T., Dunning, L., Gracie, J. A., and McInnes, I. B. (2007) Expression and proinflammatory role of proteinase-activated receptor 2 in rheumatoid synovium: ex vivo studies using a novel proteinase-activated receptor 2 antagonist. Arthritis Rheum. 56, 765-771 (Pubitemid 46399423)
26. Palmer, H. S., Kelso, E. B., Lockhart, J. C., Sommerhoff, C. P., Plevin, R., Goh, F. G., and Ferrell, W. R. (2007) Protease-activated receptor 2 mediates the proinflammatory effects of synovial mast cells. Arthritis Rheum. 56, 3532-3540 (Pubitemid 350100686)
27. McIntosh, K. A., Plevin, R., Ferrell, W. R., and Lockhart, J. C. (2007) The therapeutic potential of proteinase-activated receptors in arthritis. Curr. Opin. Pharmacol. 7, 334-338 (Pubitemid 46731190)
28. Kawabata, A., Kuroda, R., Minami, T., Kataoka, K., and Taneda, M. (1998) Increased vascular permeability by a specific agonist of protease-activated receptor-2 in rat hindpaw. Br. J. Pharmacol. 125, 419-422 (Pubitemid 28451476)
29. Kelso, E. B., Lockhart, J. C., Hembrough, T., Dunning, L., Plevin, R., Hollenberg, M. D., Sommerhoff, C. P., McLean, J. S., and Ferrell, W. R. (2006) Therapeutic promise of proteinase-activated receptor-2 antagonism in joint inflammation. J. Pharmacol. Exp. Ther. 316, 1017-1024 (Pubitemid 43345273)
30. Vergnolle, N. (1999) Proteinase-activated receptor-2-activating peptides induce leukocyte rolling, adhesion, and extravasation in vivo. J. Immunol. 163, 5064-5069
31. Nakano, S., Mishiro, T., Takahara, S., Yokoi, H., Hamada, D., Yukata, K., Takata, Y., Goto, T., Egawa, H., Yasuoka, S., Furouchi, H., Hirasaka, K., Nikawa, T., and Yasui, N. (2007) Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis. Clin. Rheumatol. 26, 1284-1292 (Pubitemid 47034184)
32. Kang, O. H., Jeong, H. J., Kim, D. K., Choi, S. C., Kim, T. H., Nah, Y. H., Kim, H. M., and Lee, Y. M. (2003) Trypsin induces tumour necrosis factor-alpha secretion from a human leukemic mast cell line. Cell Biochem. Funct. 21, 161-167
33. Woolley, D. E. (2003) The mast cell in inflammatory arthritis. N. Engl. J. Med. 348, 1709-1711
34. Ferrell, W. R., Kelso, E. B., Lockhart, J. C., Plevin, R., and McInnes, I. B. (2010) Protease-activated receptor 2: a novel pathogenic pathway in a murine model of osteoarthritis. Ann. Rheum. Dis. 69, 2051-2054
35. Shin, K., Nigrovic, P. A., Crish, J., Boilard, E., McNeil, H. P., Larabee, K. S., Adachi, R., Gurish, M. F., Gobezie, R., Stevens, R. L., and Lee, D. M. (2009) Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes. J. Immunol. 182, 647-656
36. Lee, D. M., Friend, D. S., Gurish, M. F., Benoist, C., Mathis, D., and Brenner, M. B. (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297, 1689-1692 (Pubitemid 35000781)
37. Pimentel, T. A., Sampaio, A. L., D'Acquisto, F., Perretti, M., and Oliani, S. M. (2011) An essential role for mast cells as modulators of neutrophils influx in collagen-induced arthritis in the mouse. Lab. Invest. 91, 33-42
38. Al-Ani, B., Saifeddine, M., Wijesuriya, S. J., and Hollenberg, M. D. (2002) Modified proteinase-activated receptor-1 and -2 derived peptides inhibit proteinase-activated receptor-2 activation by trypsin. J. Pharmacol. Exp. Ther. 300, 702-708
39. Kanke, T., Kabeya, M., Kubo, S., Kondo, S., Yasuoka, K., Tagashira, J., Ishiwata, H., Saka, M., Furuyama, T., Nishiyama, T., Doi, T., Hattori, Y., Kawabata, A., Cunningham, M. R., and Plevin, R. (2009) Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo. Br. J. Pharmacol. 158, 361-371
40. Barry, G. D., Le, G. T., and Fairlie, D. P. (2006) Agonists and antagonists of protease activated receptors (PARs). Curr. Med. Chem. 13, 243-265
41. Wang, J., Boerma, M., Kulkarni, A., Hollenberg, M. D., and Hauer-Jensen, M. (2010) Activation of protease activated receptor 2 by exogenous agonist exacerbates early radiation injury in rat intestine. Int. J. Radiat. Oncol. Biol. Phys. 77, 1206-1212
42. Barry, G. D., Suen, J. Y., Le, G. T., Cotterell, A., Reid, R. C., and Fairlie, D. P. (2010) Novel agonists and antagonists for human protease activated receptor 2. J. Med. Chem. 53, 7428-7440
43. Suen, J. Y., Barry, G. D., Lohman, R. J., Halili, M. A., Cotterell, A. J., Le, G. T., and Fairlie, D. P. (2012) Modulating human proteinase activated receptor 2 with a novel antagonist (GB88) and agonist (GB110). Br. J. Pharmacol. 165, 1413-1423
44. Thrivikraman, K. V., Huot, R. L., and Plotsky, P. M. (2002) Jugular vein catheterization for repeated blood sampling in the unrestrained conscious rat. Brain Res. Brain Res. Protoc. 10, 84-94 (Pubitemid 35335974)
45. van Raay, L., Morris, M. J., Reed, R. C., O'Brien, T. J., and Dedeurwaerdere, S. (2009) A novel system allowing long-term simultaneous video-electroencephalography recording, drug infusion and blood sampling in rats. J. Neurosci. Methods 179, 184-190
46. Kawabata, A., Kawao, N., Kuroda, R., Tanaka, A., and Shimada, C. (2002) The PAR-1-activating peptide attenuates carrageenan-induced hyperalgesia in rats. Peptides 23, 1181-1183 (Pubitemid 34786310)
47. Lin, H. S., Hu, C. Y., Chan, H. Y., Liew, Y. Y., Huang, H. P., Lepescheux, L., Bastianelli, E., Baron, R., Rawadi, G., and Clement-Lacroix, P. (2007) Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br. J. Pharmacol. 150, 862-872 (Pubitemid 46536628)
48. Nishikawa, M., Myoui, A., Tomita, T., Takahi, K., Nampei, A., and Yoshikawa, H. (2003) Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 48, 2670-2681 (Pubitemid 37129445)
49. Woodruff, T. M., Strachan, A. J., Dryburgh, N., Shiels, I. A., Reid, R. C., Fairlie, D. P., and Taylor, S. M. (2002) Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis Rheum. 46, 2476-2485
50. Flick, M. J., LaJeunesse, C. M., Talmage, K. E., Witte, D. P., Palumbo, J. S., Pinkerton, M. D., Thornton, S., and Degen, J. L. (2007) Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J. Clin. Invest. 117, 3224-3235 (Pubitemid 350096980)
51. Lam, D. K., and Schmidt, B. L. (2010) Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway. Pain 149, 263-272
52. Mei, H., Korfmacher, W., and Morrison, R. (2006) Rapid in vivo oral screening in rats: reliability, acceptance criteria, and filtering efficiency. AAPS J. 8, E493-E500 (Pubitemid 44207809)
53. Costa, R., Marotta, D. M., Manjavachi, M. N., Fernandes, E. S., Lima-Garcia, J. F., Paszcuk, A. F., Quintao, N. L., Juliano, L., Brain, S. D., and Calixto, J. B. (2008) Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice. Br. J. Pharmacol. 154, 1094-1103 (Pubitemid 351915068)
54. Alshurafa, H. N., Stenton, G. R., Wallace, J. L., Hollenberg, M. D., Befus, A. D., and Vliagoftis, H. (2004) A protease activated receptor-2 (PAR-2) activating peptide, tc-LIGRLO-NH2, induces protease release from mast cells: role in TNF degradation. BMC Pharmacol. 4, 12
55. Shpacovitch, V. M., Varga, G., Strey, A., Gunzer, M., Mooren, F., Buddenkotte, J., Vergnolle, N., Sommerhoff, C. P., Grabbe, S., Gerke, V., Homey, B., Hollenberg, M., Luger, T. A., and Steinhoff, M. (2004) Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices. J. Leukoc. Biol. 76, 388-398 (Pubitemid 39006953)
56. Bunnett, N. W. (2006) Protease-activated receptors: how proteases signal to cells to cause inflammation and pain. Semin. Thromb. Hemost. 32(Suppl. 1), 39-48
57. Johansson, U., Lawson, C., Dabare, M., Syndercombe-Court, D., Newland, A. C., Howells, G. L., and Macey, M. G. (2005) Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1{beta}. J. Leukoc. Biol. 78, 967-975 (Pubitemid 41384413)
58. Vergnolle, N., Hollenberg, M. D., Sharkey, K. A., and Wallace, J. L. (1999) Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw. Br. J. Pharmacol. 127, 1083-1090 (Pubitemid 29326629)
59. Steinhoff, M., Vergnolle, N., Young, S. H., Tognetto, M., Amadesi, S., Ennes, H. S., Trevisani, M., Hollenberg, M. D., Wallace, J. L., Caughey, G. H., Mitchell, S. E., Williams, L. M., Geppetti, P., Mayer, E. A., and Bunnett, N. W. (2000) Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat. Med. 6, 151-158 (Pubitemid 30082358)
60. Steinhoff, M., Neisius, U., Ikoma, A., Fartasch, M., Heyer, G., Skov, P. S., Luger, T. A., and Schmelz, M. (2003) Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J. Neurosci. 23, 6176-6180 (Pubitemid 36875617)
61. Lohman, R. J., Cotterell, A. J., Suen, J., Liu, L., Do, A. T., Vesey, D. A., and Fairlie, D. P. (2012) Antagonism of protease-activated receptor 2 protects against experimental colitis. J. Pharmacol. Exp. Ther. 340, 256-265