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Proteases and Their Receptors in Inflammation pp 275–290Cite as

Microbial Proteases: Relevance to the Inflammatory Response

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Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

As virulence factors, microbial proteases often exert dual activities, enhancing the inflammatory response and affecting leukocyte functions. By activating the kallikrein-kinin system, they induce the release of kinins, which cause vascular leakage, and by inducing C5a production from the fifth complement component, they trigger the release of histamine. Leukocytes also accumulate in response to the production of the chemoattractant C5a and the secretion of chemokines from various cells, leading to exaggerated inflammatory reactions. Conversely, microbial proteases degrade chemoattractants, including chemokines, and the leukocyte receptors essential for leukocyte infiltration and the immune responses, thereby contributing to the bacterial evasion of the host defense system and the survival of the microorganism. In this way, they contribute to modulation of the inflammation caused by microbial infections, and their activity may exacerbate infectious diseases. Therefore, the specific inhibition of microbial proteases constitutes a valid therapeutic strategy for infectious diseases.

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References

  1. Guo Y, Nguyen KA, Potempa J (2010) Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon’s knife to a meat chopper-like brutal degradation of proteins. Periodontol 2000 54:15–44

    Article  PubMed  Google Scholar 

  2. Potempa J, Pike RN (2009) Corruption of innate immunity by bacterial proteases. J Innate Immun 1:70–87

    Article  PubMed  CAS  Google Scholar 

  3. Cochrane CG, Griffin JH (1982) The biochemistry and pathophysiology of the contact system of plasma. Adv Immunol 33:241–306

    Article  PubMed  CAS  Google Scholar 

  4. Hugli TE (1984) Structure and function of the anaphylatoxins. Springer Semin Immunopathol 7:193–219

    Article  PubMed  CAS  Google Scholar 

  5. Bhoola KD, Figueroa CD, Worthy K (1992) Bioregulation of kinins: Kallikreins, kininogens, and kininases. Pharmacol Rev 44:1–80

    PubMed  CAS  Google Scholar 

  6. Leeb-Lundberg LMF, Marceau F, Müller-Ester W, Pettibone D, Zuraw B (2005) International union of pharmacology XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 57:27–77

    Article  PubMed  CAS  Google Scholar 

  7. Chen Z, Potempa J, Polanowski A, Wikström M, Travis J (1992) Purification of and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis. J Biol Chem 267:18896–18901

    PubMed  CAS  Google Scholar 

  8. Pike R, McGraw W, Potempa J, Travis J (1994) Lysine- and arginine-specific proteinases from Porphyromonas gingivalis: isolation, characterization, and evidence for the existence of complexes with hemoagglutinins. J Biol Chem 269:406–411

    PubMed  CAS  Google Scholar 

  9. Imamura T, Pike RN, Potempa J, Travis J (1994) Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway. J Clin Invest 94:361–367

    Article  PubMed  CAS  Google Scholar 

  10. Molla A, Yamamoto T, Akaike T, Miyoshi S, Maeda H (1989) Activation of Hageman factor and prekallikrein and generation of kinin by various microbial proteinases. J Biol Chem 264:10589–10594

    PubMed  CAS  Google Scholar 

  11. Miyoshi S, Shinoda S (1992) Activation mechanism of human Hageman factor-plasma kallikrein-kinin system by Vibrio vulnificus metalloproteases. FEBS Lett 308:515–519

    Article  Google Scholar 

  12. Vargaftig BB, Giroux EL (1976) Mechanism of clostripain-induced kinin release from human, rat, and canine plasma. Adv Exp Med Biol 70:157–175

    PubMed  CAS  Google Scholar 

  13. Jones BL, Wilcox MH (1995) Aeromonas infection and their treatment. J Antimicrob Chemother 35:453–461

    Article  PubMed  CAS  Google Scholar 

  14. Imamura T, Kobayashi H, Khan R, Nitta H, Okamoto K (2006) Induction of vascular leakage and blood pressure lowering through kinin release by a serine protease from Aeromonas sobria. J Immunol 177:8723–8729

    PubMed  CAS  Google Scholar 

  15. Brenner Z (1973) Biology of Trypanosoma Cruzi. Annu Rev Microbiol 27:347–382

    Article  Google Scholar 

  16. Del Nery E, Juliano MA, Lima APCA, Scharfstein JL (1997) Kininogenase activity by the major cysteinyl proteinase (Cruzipain) from Tripanosoma cruzi. J Biol Chem 272:25713–25718

    Article  PubMed  CAS  Google Scholar 

  17. Imamura T, Tanase S, Szmyd G, Kozik A, Travis J, Potempa J (2005) Induction of vascular leakage through bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus. J Exp Med 201:1669–1676

    Article  PubMed  CAS  Google Scholar 

  18. Herwald H, Collin M, Müller-Ester W, Björck L (1996) Streptococcal cysteine proteinase releases kinins: a novel virulence mechanism. J Exp Med 184:665–673

    Article  PubMed  CAS  Google Scholar 

  19. Potempa J, Dubin A, Korzus G, Travis J (1988) Degradation of elastin by a cysteine proteinase from Staphylococcus aureus. J Biol Chem 263:2664–2667

    PubMed  CAS  Google Scholar 

  20. Maruo K, Akaike T, Inada Y, Ohkubo I, Ono T, Maeda H (1993) Effect of microbial and mite proteases on low and high molecular weight kininogens. Generation of kinin and inactivation of thiol protease inhibitory activity. J Biol Chem 268:17711–17715

    PubMed  CAS  Google Scholar 

  21. Miyamoto T, Oshima S, Ishizaki T, Sato S (1968) Allergenic identity between the common floor mite (Dermatophagoides farinae, Hughes, 1961) and house dust as a causative antigen in bronchial asthma. J Allergy 42:14–28

    Article  PubMed  CAS  Google Scholar 

  22. Maruo K, Akaike T, Matsumura Y, Kohmoto S, Inada Y, Ono T, Arao T, Maeda H (1991) Triggering of the vascular permeability reaction by activation of the Hageman factor-prekallikrein system by house dust mite proteinase. Biochim Biophys Acta 1074:62–68

    PubMed  CAS  Google Scholar 

  23. Marceau F, Hess JF, Bachvarov DR (1998) The B1 receptors for kinins. Pharmacol Rev 50:357–386

    PubMed  CAS  Google Scholar 

  24. Imamura T, Pike RN, Potempa J, Travis J (1995) Dependence of vascular permeability enhancement on cysteine proteinases in vesicles of Porphyromonas gingivalis. Infect Immun 63:1999–2003

    PubMed  CAS  Google Scholar 

  25. Regoli D, Barabé J (1980) Pharmacology of bradykinin and related kinins. Pharmacol Rev 32:1–46

    PubMed  CAS  Google Scholar 

  26. Hu SW, Huang CH, Huang HC, Lai YY, Lin YY (2006) Transvascular dissemination of Porphyromonas gingivalis from a sequestered site is dependent upon activation of the kallikrein/kinin pathway. J Periodontal Res 32:200–207

    Article  Google Scholar 

  27. Hugli TE (1986) Biochemistry and biology of anaphylatoxins. Complement 3:111–127

    PubMed  CAS  Google Scholar 

  28. Nitta H, Imamura T, Wada Y, Irie A, Kobayashi H, Okamoto K, Baba H (2008) Production of C5a by ASP, a serine protease released from Aeromonas sobria. J Immunol 181:3602–3608

    PubMed  CAS  Google Scholar 

  29. Wöhrl S, Hemmer W, Focke M, Rappersberger K, Jarisch R (2004) Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine. Allergy Asthma Proc 25:305–311

    PubMed  Google Scholar 

  30. Feng BS, He SH, Zhang PY, Wu L, Yang PC (2007) Mast cells play a crucial role in Staphylococcus aureus peptidoglycan-induced diarrhea. Am J Pathol 171:537–547

    Article  PubMed  CAS  Google Scholar 

  31. Janda JM, Duffey PS (1988) Mesophilic aeromonads in human disease: current toxanomy, laboratory identification, and infectious disease spectrum. Rev Infect Dis 10:980–997

    Article  PubMed  CAS  Google Scholar 

  32. Deutsch SF, Wedzina W (1997) Aeromonas sobria-associated left-sided segmental colitis. Am J Gastroenterol 92:2104–2106

    PubMed  CAS  Google Scholar 

  33. Janda JM, Abbott SL (1998) Evoling concepts regarding the genus Aeromonas: an expanding panorama of species, disease presentations, and unanswered questions. Clin Infect Dis 27:332–344

    Article  PubMed  CAS  Google Scholar 

  34. Wingrove JA, DiScipio RG, Chen Z, Potempa J, Travis J, Hugli TE (1992) Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis. J Biol Chem 267:18902–18907

    PubMed  CAS  Google Scholar 

  35. DiScipio RG, Daffern PJ, Kawahara M, Pike R, Travis J, Hugli TE (1996) Cleavage of human complement component C5 by cysteine proteinases from Porphyromonas (Bacteroides) gingivalis. Prior oxidation of C5 augments proteinase digestion of C5. Immunology 87:660–667

    Article  PubMed  CAS  Google Scholar 

  36. Maruo K, Akaike T, Ono T, Okamoto T, Maeda H (1997) Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease. J Allergy Clin Immunol 100:253–260

    Article  PubMed  CAS  Google Scholar 

  37. Uehara A, Naito M, Imamura T, Potempa J, Travis J, Nakayama K, Takada H (2008) Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis. J Med Microbiol 57:500–507

    Article  PubMed  CAS  Google Scholar 

  38. Uehara A, Imamura T, Potempa J, Travis J, Takada H (2008) Gingipains from Prophyromonas gingivalis synergistically induce the production of proinflammatory cytokines through protease-activated receptors with Toll-like and NOD1/2 ligands in human monocytic cells. Cell Microbiol 10:1181–1189

    Article  PubMed  CAS  Google Scholar 

  39. Oido-Mori M, Rezzonico R, Wang P-L, Kowashi Y, Dayer J-M, Baehni PC, Chizzolini C (2001) Porphyromonas gingivalis gingipain-R enhances interleukin-8 but decreases gamma interferon-inducible protein 10 production by human gingival fibroblasts in response to T-cell contact. Infect Immun 69:4493–4501

    Article  PubMed  CAS  Google Scholar 

  40. Niederfuhr A, Kirsche H, Deutschle T, Poppert S, Riechelmann H, Wellinghausen N (2008) Staphylococcus aureus in nasal lavage and biopsy of patients with chronic rhinosinusitis. Allergy 63:1359–1367

    Article  PubMed  CAS  Google Scholar 

  41. Rudack C, Sachse F, Albert N, Becker K, von Eiff C (2009) Immunomodulation of nasal epithelial cells by Staphylococcus aureus-derived serine proteases. J Immunol 183:7592–7601

    Article  PubMed  CAS  Google Scholar 

  42. Kida Y, Higashimoto Y, Inoue H, Shimizu T, Kuwano K (2008) A novel protease from Pseudomonas aeruginosa activates NF-κB through protease-activated receptors. Cell Microbiol 10:1491–1504

    Article  PubMed  CAS  Google Scholar 

  43. Asokananthan N, Graham PT, Stewart DJ, Bakker AJ, Eidne KA, Thompson PJ, Stewart GA (2002) House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells: the cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1. J Immunol 169:4572–4578

    PubMed  CAS  Google Scholar 

  44. Dulon S, Leduc D, Cottrell GS, D’Alayer J, Hansen KK, Bunnett NW, Hollenberg MD, Pidard D, Chignard M (2005) Pseudomonas aeruginosa elastase disables proteinase-activated receptor 2 in respiratory epithelial cells. Am J Respir Cell Mol Biol 32:411–419

    Article  PubMed  CAS  Google Scholar 

  45. Puthia MK, Lu J, Tan KSW (2008) Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kB-dependent manner. Eukaryotic Cell 7:435–443

    Article  PubMed  CAS  Google Scholar 

  46. Yu Y, Chadee K (1997) Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact. Gastroenterology 112:1536–1547

    Article  PubMed  CAS  Google Scholar 

  47. Mikolajczyk-Pawlinska J, Travis J, Potempa J (1998) Modulation of interleukin-8 activity by gingipains from Porphyromonas gingivalis: implications for pathogenicity of periodontal disease. FEBS Lett 440:282–286

    Article  PubMed  CAS  Google Scholar 

  48. Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V, Peled A, Hanski E (2006) A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues. EMBO J 25:4028–4037

    Article  Google Scholar 

  49. Edwards RJ, Taylor GW, Ferguson M, Murray S, Rendell N, Wrigley A, Bai Z, Boyle J, Finny SJ, Jones A et al (2005) Specific C-terminal cleavage and inactivation of interleukin-8 by invasive isolates of Streptococcus pyogenes. J Infect Dis 192:782–790

    Article  Google Scholar 

  50. Wexler DE, Cleary PP (1985) Purification and characteristics of the streptococcal chemotactic factor inactivator. Infect Immun 50:757–764

    PubMed  CAS  Google Scholar 

  51. Bohnsack JF, Mollison KW, Buko AM, Ashworth JC, Hill HR (1991) Group B streptococci inactivate C5a by enzymatic cleavage at the carboxy terminus. Biochem J 273:635–640

    PubMed  CAS  Google Scholar 

  52. O’Conner SP, Cleary PP (1986) Localization of the streptococcal C5a peptidase to the surface of group A streptococci. Infect Immun 53:432–434

    Google Scholar 

  53. Chen C, Cleary P (1990) Complete nucleotide sequence of the streptococcal C5a peptidase gene of Streptococcus pyogenes. J Biol Chem 265:3161–3167

    PubMed  CAS  Google Scholar 

  54. Ji Y, McKandsborough L, Kondagunta A, Cleary PP (1996) C5a peptidase alters clearance and trafficking of group A streptococcus by infected mice. Infect Immun 64:503–510

    PubMed  CAS  Google Scholar 

  55. Sumby P, Zhang S, Whitney A, Falugi F, Grandi G, Graviss EA, DeLeo FR, Musser JM (2008) A chemokine-degrading extracellular protease made by group A Streptococcus alters pathogenesis by enhancing evasion of the innate immune response. Infect Immun 76:978–985

    Article  PubMed  CAS  Google Scholar 

  56. Jagels MA, Travis J, Potempa J, Pike R, Hugli TE (1996) Proteolytic inactivation of the leukocyte C5a receptor by proteinases derived from Porphyromonas gingivalis. Infect Immun 64:1984–1991

    PubMed  CAS  Google Scholar 

  57. Sugawara S, Nemoto E, Tada H, Miyake K, Imamura T, Takada H (2000) Proteolysis of human monocyte CD14 by cysteine proteinases (Gingipains) from Porphyromonas gingivalis leading to LPS-hyporesponsiveness. J Immunol 165:411–418

    PubMed  CAS  Google Scholar 

  58. Kitamura Y, Yoneda M, Imamura T, Matono S, Aida Y, Hirofuji T, Maeda K (2002) Gingipains in the culture supernatant of Porphyromonas gingivalis cleave CD4 and CD8 on human T cells. J Periodont Res 37:464–468

    Article  PubMed  CAS  Google Scholar 

  59. Okada H, Kasai Y, Kida T (1984) T lymphocyte subsets in the inflamed gingiva of human adult periodontitis. J Periodont Res 19:595–598

    Article  PubMed  CAS  Google Scholar 

  60. Stoufi ED, Taubman MA, Ebersole JL, Smith DJ, Stashenko PP (1987) Phenotype analyses of mononuclear cells recovered from healthy and diseased human periodontal tissues. J Clin Immunol 7:235–245

    Article  PubMed  CAS  Google Scholar 

  61. Kharazmi A, Nielsen H (1991) Inhibition of human monocyte chemotaxis and chemiluminescence by Pseudomonas aeruginosa elastase. Acta Pathol Microbiol Immunol Scand 99:93–95

    CAS  Google Scholar 

  62. Leduc D, Beaufort N, de Bentzmann S, Rousselle JC, Namane A, Chignard M, Pidard D (2007) The Pseudomonas aeruginosa LasB metalloproteinase regulates the human urokinase-type plasminogen activator receptor through domain-specific endoproteolysis. Infect Immun 75:3848–3858

    Article  PubMed  CAS  Google Scholar 

  63. Lourbakos A, Potempa J, Travis J, D’Andrea MR, Andrade-Gordon P, Santulli R, Mackie E, Pike RN (2001) Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion. Infect Immun 69:5121–5130

    Article  PubMed  CAS  Google Scholar 

  64. Tancharoen S, Sarker KP, Imamura T, Biswas KK, Matsushita K, Tatsuyama S, Travis J, Potempa J, Torii M, Maruyama I (2005) Neuropeptide release from dental pulp cells by RgpB via proteinase-activated receptor-2 signaling. J Immunol 174:5796–5804

    PubMed  CAS  Google Scholar 

  65. Holzhausen M, Spolidorio LC, Ellen RP, Jobin MC, Steinhoff M, Andrade-Gordon P, Vergnolle N (2006) Protease-activated receptor-2 activation: a major role in the pathogenesis of Porphyromonas gingivalis infection. Am J Pathol 168:1189–1199

    Article  PubMed  CAS  Google Scholar 

  66. Wong DM, Tam V, Lam R, Walsh KA, Tatarczuch L, Pagel CN, Reynolds EC, O’Brien-Simpson NM, Mackie EJ, Pike RN (2010) Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis. Infect Immun 78:629–638

    Article  PubMed  CAS  Google Scholar 

  67. Holzhausen M, Cortelli JR, da Silva VA, Franco GC, Cortelli SC, Vergnolle N (2010) Protease-activated receptor-2 (PAR-2) in human periodontitis. J Dent Res 89:948–953

    Article  PubMed  CAS  Google Scholar 

  68. Yasuhara R, Miyamoto Y, Imamura T, Potempa J, Yoshimura K, Kamijo K (2009) Lysine-specific gingipain promotes lipopolysaccharide- and active vitamin D3-induced osteoclast differentiation by degrading osteoprotegerin. Biochem J 419:159–166

    Article  PubMed  CAS  Google Scholar 

  69. Tada H, Sugawara S, Nemoto E, Imamura T, Potempa J, Travis J, Shimauchi H, Takada H (2003) Proteplysis of ICAM-1 on human oral epithelial cells by gingipains. J Dent Res 82:796–801

    Article  PubMed  CAS  Google Scholar 

  70. Tada H, Sugawara S, Nemoto E, Takahashi N, Imamura T, Potempa J, Travis J, Shimauchi H, Takada H (2002) Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production. Infect Immun 70:3304–3307

    Article  PubMed  CAS  Google Scholar 

  71. Giacaman RA, Nobbs AH, Ross KF, Herzberg MC (2007) Porphyromonas gingivalis selectively up-regulates the HIV-1 coreceptor CCR5 in oral keratinocytes. J Immunol 179:2542–2550

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Pathology, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan

    Takahisa Imamura

  2. Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, 30-387, Poland

    Jan Potempa

  3. Oral Health and Systemic Diseases Research Group, University of Louisville School of Dentistry, Louisville, KY, 40202, USA

    Jan Potempa

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  1. Takahisa Imamura
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  2. Jan Potempa
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Correspondence to Jan Potempa .

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Editors and Affiliations

  1. CHU Purpan, INSERM U 563, BP 3028, Toulouse Cedex, 31024, France

    Nathalie Vergnolle

  2. Institut Pasteur, Unite de Defense Innee et Inflammation, INSERM U 874, Rue du Dr. Roux 25, Paris Cedex 15, 75724, France

    Michel Chignard

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Imamura, T., Potempa, J. (2011). Microbial Proteases: Relevance to the Inflammatory Response. In: Vergnolle, N., Chignard, M. (eds) Proteases and Their Receptors in Inflammation. Progress in Inflammation Research. Springer, Basel. https://doi.org/10.1007/978-3-0348-0157-7_12

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  • DOI: https://doi.org/10.1007/978-3-0348-0157-7_12

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