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Asthma, mast cells, mediators, allergy

정세규|이승헌|이상은
연세대학교의과대학 (Yonsei University College of Medicine)|2010.11|Yonsei Medical Journal|제51권 제6호|pp. 808-822

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Atopic dermatitisproteaseprotease-activated receptor-2 (PAR-2)
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초록

Proteases in the skin are essential to epidermal permeability barrier homeostasis. In addition to their direct proteolytic effects, certain proteases signal to cells by activating protease-activated receptors (PARs), the G-protein-coupled receptors. The expression of functional PAR-2 on human skin and its role in inflammation,pruritus, and skin barrier homeostasis have been demonstrated. Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by genetic barrier defects and allergic inflammation, which is sustained by gene-environmental interactions. Recent studies have revealed aberrant expression and activation of serine proteases and PAR-2 in the lesional skin of AD patients. The imbalance between proteases and protease inhibitors associated with genetic defects in the protease/protease inhibitor encoding genes, increase in skin surface pH, and exposure to proteolytically active allergens contribute to this aberrant protease/PAR-2 signaling in AD. The increased protease activity in AD leads to abnormal desquamation, degradation of lipid-processing enzymes and antimicrobial peptides, and activation of primary cytokines, thereby leading to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Moreover, up-regulated proteases stimulate PAR-2 in lesional skin of AD and lead to the production of cytokines and chemokines involved in inflammation and immune responses, itching sensation, and sustained epidermal barrier perturbation with easier allergen penetration. In addition, PAR-2 is an important sensor for exogenous danger molecules, such as exogenous proteases from various allergens,and plays an important role in AD pathogenesis. Together, these findings suggest that protease activity or PAR-2 may be a future target for therapeutic intervention for the treatment of AD.

Abstract

Proteases in the skin are essential to epidermal permeability barrier homeostasis. In addition to their direct proteolytic effects, certain proteases signal to cells by activating protease-activated receptors (PARs), the G-protein-coupled receptors. The expression of functional PAR-2 on human skin and its role in inflammation,pruritus, and skin barrier homeostasis have been demonstrated. Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by genetic barrier defects and allergic inflammation, which is sustained by gene-environmental interactions. Recent studies have revealed aberrant expression and activation of serine proteases and PAR-2 in the lesional skin of AD patients. The imbalance between proteases and protease inhibitors associated with genetic defects in the protease/protease inhibitor encoding genes, increase in skin surface pH, and exposure to proteolytically active allergens contribute to this aberrant protease/PAR-2 signaling in AD. The increased protease activity in AD leads to abnormal desquamation, degradation of lipid-processing enzymes and antimicrobial peptides, and activation of primary cytokines, thereby leading to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Moreover, up-regulated proteases stimulate PAR-2 in lesional skin of AD and lead to the production of cytokines and chemokines involved in inflammation and immune responses, itching sensation, and sustained epidermal barrier perturbation with easier allergen penetration. In addition, PAR-2 is an important sensor for exogenous danger molecules, such as exogenous proteases from various allergens,and plays an important role in AD pathogenesis. Together, these findings suggest that protease activity or PAR-2 may be a future target for therapeutic intervention for the treatment of AD.

참고문헌 (112)

  1. Richard I, "The genetic and molecular bases of monogenic disorders affecting proteolytic systems", J Med Genet, 42, pp.529~539 (2005)
  2. Ramachandran R, "Proteinases and signalling:pathophysiological and therapeutic implications via PARs and more", Br J Pharmacol, 153, pp.S263~282 (2008)
  3. Brattsand M, "Purification, molecular cloning, and expression of a human stratum corneum trypsin-like serine protease with possible function in desquamation", J Biol Chem, 274, pp.30033~30040 (1999)
  4. Hansson L, "Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase", J Biol Chem, 269, pp.19420~19426 (1994)
  5. Bernard D, "Analysis of proteins with caseinolytic activity in a human stratum corneum extract revealed a yet unidentified cysteine protease and identified the so-called “stratum corneum thiol protease” as cathepsin l2", J Invest Dermatol, 120, pp.592~600 (2003)
  6. Horikoshi T, "Isoforms of cathepsin D and human epidermal differentiation", Biochimie, 80, pp.605~612 (1998)
  7. Hachem JP, "Serine protease signaling of epidermal permeability barrier homeostasis", J Invest Dermatol, 126, pp.2074~2086 (2006)
  8. Rattenholl A, "Role of proteinase-activated receptors in cutaneous biology and disease", Drug Dev Res, 59, pp.408~416 (2003)
  9. Hansen KK, "Proteinases as hormones: targets and mechanisms for proteolytic signaling", Biol Chem, 389, pp.971~982 (2008)
  10. Rattenholl A, "Proteinase-activated receptor-2 in the skin: receptor expression, activation and function during health and disease", Drug News Perspect, 21, pp.369~381 (2008)
  11. Demerjian M, "Acute modulations in permeability barrier function regulate epidermal cornification: role of caspase-14 and the protease-activated receptor type 2", Am J Pathol, 172, pp.86~97 (2008)
  12. Jeong SK, "Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery", J Invest Dermatol, 128, pp.1930~1939 (2008)
  13. Eissa A, "Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions", Biol Chem, 389, pp.669~680 (2008)
  14. Stefansson K, "Activation of proteinase-activated receptor-2 by human kallikrein-related peptidases", J Invest Dermatol, 128, pp.18~25 (2008)
  15. Descargues P, "Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsinlike hyperactivity in Netherton syndrome", J Invest Dermatol, 126, pp.1622~1632 (2006)
  16. Komatsu N, "Elevated human tissue kallikrein levels in the stratum corneum and serum of peeling skin syndrome-type B patients suggests an over-desquamation of corneocytes", J Invest Dermatol, 126, pp.2338~2342 (2006)
  17. Komatsu N, "Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients", Exp Dermatol, 16, pp.513~519 (2007)
  18. Komatsu N, "Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy", Br J Dermatol, 156, pp.875~883 (2007)
  19. Lundwall A, "Kallikrein-related peptidases", Cell Mol Life Sci, 65, pp.2019~2038 (2008)
  20. Caubet C, "Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE", KLK5, KLK7, pp.hK7, J Invest Dermatol[DOI]
  21. Hachem JP, "Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity", J Invest Dermatol, 125, pp.510~520 (2005)
  22. Yamasaki K, "Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin", FASEB J, 20, pp.2068~2080 (2006)
  23. Ekholm IE, "Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process?", J Invest Dermatol, 114, pp.56~63 (2000)
  24. Brattsand M, "A proteolytic cascade of kallikreins in the stratum corneum", J Invest Dermatol, 124, pp.198~203 (2005)
  25. Elias PM, "The secretory granular cell: the outermost granular cell as a specialized secretory cell", J Investig Dermatol Symp Proc, 3, pp.87~100 (1998)
  26. Yoon H, "Activation profiles and regulatory cascades of the human kallikrein-related peptidases", J Biol Chem, 282, pp.31852~31864 (2007)
  27. Oikonomopoulou K, "Proteinase-activated receptors, targets for kallikrein signaling", J Biol Chem, 281, pp.32095~32112 (2006)
  28. Komatsu N, "Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases", Br J Dermatol, 153, pp.274~281 (2005)
  29. Kishibe M, "Kallikrein 8 is involved in skin desquamation in cooperation with other kallikreins", J Biol Chem, 282, pp.5834~5841 (2007)
  30. Morizane S, "Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid", J Invest Dermatol, 130, pp.1297~1306 (2010)
  31. Ovaere P, "The emerging roles of serine protease cascades in the epidermis", Trends Biochem Sci, 34, pp.453~463 (2009)
  32. List K, "Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase", MT-SP1, 2003, pp.163, 901~910
  33. Mitsudo K, "Inhibition of serine proteinases plasmin, trypsin, subtilisin A, cathepsin G, and elastase by LEKTI: a kinetic analysis", Biochemistry, 42, pp.3874~3881 (2003)
  34. Roelandt T, "LEKTI-1 in sickness and in health", Int J Cosmet Sci, 31, pp.247~254 (2009)
  35. Meyer-Hoffert U, "Identification of lymphoepithelial Kazal-type inhibitor 2 in human skin as a kallikreinrelated peptidase 5-specific protease inhibitor", PLoS One, 4, pp.e4372~ (2009)
  36. Galliano MF, "A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis", J Biol Chem, 281, pp.5780~5789 (2006)
  37. Oberst MD, "HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease", Am J Physiol Cell Physiol, 289, pp.C462~470 (2005)
  38. Oberst MD, "The activation of matriptase requires its noncatalytic domains, serine protease domain, and its cognate inhibitor", J Biol Chem, 278, pp.26773~26779 (2003)
  39. Kawabata A, "PAR-2: structure, function and relevance to human diseases of the gastric mucosa", Expert Rev Mol Med, 4, pp.1~17 (2002)
  40. Steinhoff M, "Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase", Exp Dermatol, 8, pp.282~294 (1999)
  41. Steinhoff M, "Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin", J Neurosci, 23, pp.6176~6180 (2003)
  42. Scott G, "Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation", J Invest Dermatol, 117, pp.1412~1420 (2001)
  43. Déry O, "Trafficking of proteinase-activated receptor-2 and beta-arrestin-1 tagged with green fluorescent protein. beta-Arrestin-dependent endocytosis of a proteinase receptor", J Biol Chem, 274, pp.18524~18535 (1999)
  44. Santulli RJ, "Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes", Proc Natl Acad Sci U S A, 92, pp.9151~9155 (1995)
  45. Derian CK, "Differential regulation of human keratinocyte growth and differentiation by a novel family of protease-activated receptors", Cell Growth Differ, 8, pp.743~749 (1997)
  46. Scott IR, "Histidine-rich protein of the keratohyalin granules. Source of the free amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum", Biochim Biophys Acta, 719, pp.110~117 (1982)
  47. McGrath JA, "The filaggrin story: novel insights into skinbarrier function and disease", Trends Mol Med, 14, pp.20~27 (2008)
  48. Denecker G, "Caspase-14 protects against epidermal UVB photodamage and water loss", Nat Cell Biol, 9, pp.666~674 (2007)
  49. Resing KA, "Characterization of profilaggrin endoproteinase 1. A regulated cytoplasmic endoproteinase of epidermis", J Biol Chem, 270, pp.28193~28198 (1995)
  50. Yamazaki M, "Cytoplasmic processing of human profilaggrin by active mu-calpain", Biochem Biophys Res Commun, 235, pp.652~656 (1997)
  51. Pearton DJ, "Proprotein convertase expression and localization in epidermis: evidence for multiple roles and substrates", Exp Dermatol, 10, pp.193~203 (2001)
  52. Leyvraz C, "The epidermal barrier function is dependent on the serine protease CAP1", Prss8, 2005, pp.170, 487~496
  53. Netzel-Arnett S, "Evidence for a matriptase-prostasin proteolytic cascade regulating terminal epidermal differentiation", J Biol Chem, 281, pp.32941~32945 (2006)
  54. Borgon ̃o CA, "A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation", J Biol Chem, 282, pp.3640~3652 (2007)
  55. Deraison C, "LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pHdependent interaction", Mol Biol Cell, 18, pp.3607~3619 (2007)
  56. Zeeuwen PL, "The biology of cystatin M", E and its cognate target proteases, 2009, pp.129, 1327~1338
  57. Cheng T, "Cystatin M", E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M, J Biol Chem, pp.2006, 281[DOI]
  58. Cheng T, "The cystatin M", E-controlled pathway of skin barrier formation: expression of its key components in psoriasis and atopic dermatitis, 2009, pp.161, 253~264
  59. Lai Y, "AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense", Trends Immunol, 30, pp.131~141 (2009)
  60. Aberg KM, "Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers", J Invest Dermatol, 128, pp.917~925 (2008)
  61. Yamasaki K, "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea", Nat Med, 13, pp.975~980 (2007)
  62. Seeliger S, "Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo", FASEB J, 17, pp.1871~1885 (2003)
  63. Iwakiri K, "Human airway trypsin-like protease induces PAR-2-mediated IL-8 release in psoriasis vulgaris", J Invest Dermatol, 122, pp.937~944 (2004)
  64. Feingold KR, "The regulation of permeability barrier homeostasis", J Invest Dermatol, 127, pp.1574~1576 (2007)
  65. Denda M, "trans-4-(Aminomethyl)cyclohexane carboxylic acid (T-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans", J Invest Dermatol, 109, pp.84~90 (1997)
  66. Steinhoff M, "Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response", Endocr Rev, 26, pp.1~43 (2005)
  67. Buddenkotte J, "Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-kappa B", J Invest Dermatol, 124, pp.38~45 (2005)
  68. Wakita H, "Thrombin and trypsin induce granulocyte-macrophage colony-stimulating factor and interleukin-6 gene expression in cultured normal human keratinocytes", Proc Assoc Am Physicians, 109, pp.190~207 (1997)
  69. Hou L, "Immunolocalization of protease-activated receptor-2 in skin: receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro", Immunology, 94, pp.356~362 (1998)
  70. Kawagoe J, "Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear", Jpn J Pharmacol, 88, pp.77~84 (2002)
  71. Liu YJ, "TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation", Annu Rev Immunol, 25, pp.193~219 (2007)
  72. Yoo J, "Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin", J Exp Med, 202, pp.541~549 (2005)
  73. Ziegler SF, "Thymic stromal lymphopoietin in normal and pathogenic T cell development and function", Nat Immunol, 7, pp.709~714 (2006)
  74. Briot A, "Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome", J Exp Med, 206, pp.1135~1147 (2009)
  75. Steinhoff M, "Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism", Nat Med, 6, pp.151~158 (2000)
  76. Paus R, "Frontiers in pruritus research: scratching the brain for more effective itch therapy", J Clin Invest, 116, pp.1174~1186 (2006)
  77. Steinhoff M, "Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus", J Invest Dermatol, 126, pp.1705~1718 (2006)
  78. Costa R, "Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice", Br J Pharmacol, 154, pp.1094~1103 (2008)
  79. Steinhoff M, "Modern aspects of cutaneous neurogenic inflammation", Arch Dermatol, 139, pp.1479~1488 (2003)
  80. Komatsu N, "Quantification of eight tissue kallikreins in the stratum corneum and sweat", J Invest Dermatol, 126, pp.925~929 (2006)
  81. Amadesi S, "Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia", J Neurosci, 24, pp.4300~4312 (2004)
  82. Vasilopoulos Y, "Genetic association between an AACC insertion in the 3’UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis", J Invest Dermatol, 123, pp.62~66 (2004)
  83. Hansson L, "Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis", J Invest Dermatol, 118, pp.444~449 (2002)
  84. Walley AJ, "Gene polymorphism in Netherton and common atopic disease", Nat Genet, 29, pp.175~178 (2001)
  85. Mägert HJ, "LEKTI, a novel 15-domain type of human serine proteinase inhibitor", J Biol Chem, 274, pp.21499~21502 (1999)
  86. Hachem JP, "Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome", J Invest Dermatol, 126, pp.1609~1621 (2006)
  87. Descargues P, "Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity", Nat Genet, 37, pp.56~65 (2005)
  88. Bonnart C, "Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing", J Clin Invest, 120, pp.871~882 (2010)
  89. Kato A, "Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population", Br J Dermatol, 148, pp.665~669 (2003)
  90. Vasilopoulos Y, "A nonsynonymous substitution of cystatin A, a cysteine protease inhibitor of house dust mite protease, leads to decreased mRNA stability and shows a significant association with atopic dermatitis", Allergy, 62, pp.514~519 (2007)
  91. Mauro T, "SC pH: measurement, origins, and functions. In Skin Barrier.", pp.223~230 (2006), Taylor & Francis Group
  92. Fluhr JW, "Stratum corneum acidification in neonatal skin: secretory phospholipase A2 and the sodium", hydrogen antiporter-1 acidify neonatal rat stratum corneum, 2004, pp.122, 320~329
  93. Schmid-Wendtner MH, "The pH of the skin surface and its impact on the barrier function", Skin Pharmacol Physiol, 19, pp.296~302 (2006)
  94. Rippke F, "Stratum corneum pH in atopic dermatitis: impact on skin barrier function and colonization with Staphylococcus Aureus", Am J Clin Dermatol, 5, pp.217~223 (2004)
  95. Palmer CN, "Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis", Nat Genet, 38, pp.441~446 (2006)
  96. O’Regan GM, "Filaggrin in atopic dermatitis", J Allergy Clin Immunol, 122, pp.689~693 (2008)
  97. Fluhr JW, "Is the filaggrin-histidine-urocanic acid pathway essential for stratum corneum acidification?", J Invest Dermatol, 130, pp.2141~2144 (2010)
  98. Roelandt T, "Proteolytically active allergens cause barrier breakdown", J Invest Dermatol, 128, pp.1878~1880 (2008)
  99. Kato T, "Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes", Allergy, 64, pp.1366~1374 (2009)
  100. Hirasawa Y, "Staphylococcus aureus extracellular protease causes epidermal barrier dysfunction", J Invest Dermatol, 130, pp.614~617 (2010)
  101. Ohnemus U, "Regulation of epidermal tight-junctions (TJ) during infection with exfoliative toxin-negative Staphylococcus strains", J Invest Dermatol, 128, pp.906~916 (2008)
  102. Wan H, "Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions", J Clin Invest, 104, pp.123~133 (1999)
  103. Runswick S, "Pollen proteolytic enzymes degrade tight junctions", Respirology, 12, pp.834~842 (2007)
  104. Kawabata A, "Physiology and pathophysiology of proteinase-activated receptors (PARs): PARs in the respiratory system: cellular signaling and physiological", pathological roles, 2005, pp.97, 20~24
  105. Ferrell WR, "Essential role for proteinase-activated receptor-2 in arthritis", J Clin Invest, 111, pp.35~41 (2003)
  106. Hyun E, "Protease-activated receptor-2 activation: a major actor in intestinal inflammation", Gut, 57, pp.1222~1229 (2008)
  107. Kim H, "The relationship of PAR2 and pruritus in end stage renal disease patients and the clinical effectiveness of soybean extracts containing moisturizer on epidermal permeability barrier in end stage renal disease patients", J Invest Dermatol, 130, pp.S56~ (2010)
  108. Akiyama T, "Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch", Pain 2010 Aug 13., ~
  109. Kelso EB, "Therapeutic promise of proteinase-activated receptor-2 antagonism in joint inflammation", J Pharmacol Exp Ther, 316, pp.1017~1024 (2006)
  110. Kelso EB, "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, pp.765~771 (2007)
  111. Kanke T, "Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo", Br J Pharmacol, 158, pp.361~371 (2009)
  112. Goh FG, "Dual effect of the novel peptide antagonist K-14585 on proteinase-activated receptor-2-mediated signalling", Br J Pharmacol, 158, pp.1695~1704 (2009)

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