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Abstract

Oral epithelia are constantly exposed to non-pathogenic (commensal) bacteria, but generally remain healthy and uninflamed. , an oral commensal bacterium, strongly induces human -defensin-2 (hBD2), an antimicrobial and immunomodulatory peptide, in gingival epithelial cells (GECs). hBD2 is also expressed in normal oral tissue leading to the hypothesis that oral epithelia are in an activated state with respect to innate immune responses under normal conditions. In order to test this hypothesis, global gene expression was evaluated in GECs in response to stimulation by an cell wall (FnCW) preparation and to hBD2 peptide. FnCW treatment altered 829 genes, while hBD2 altered 209 genes (<0.005, ANOVA). Many induced genes were associated with the gene ontology categories of immune responses and defence responses. Consistent with the hypothesis, similar responses were activated by commensal bacteria and hBD2. These responses included up-regulation of common antimicrobial effectors and chemokines, and down-regulation of proliferation markers. In addition, FnCW up-regulated multiple protease inhibitors, and suppressed NF-B function and the ubiquitin/proteasome system. These global changes may protect the tissue from inflammatory damage. Both FnCW and hBD2 also up-regulated genes that may enhance the epithelial barrier. The findings suggest that both commensal bacteria and hBD2 activate protective responses of GECs and play an important role in immune modulation in the oral cavity.

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2007-07-01
2019-11-12
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References

  1. Al-Shahrour, F., Minguez, P., Vaquerizas, J. M., Conde, L. & Dopazo, J. ( 2005; ). babelomics: a suite of web tools for functional annotation and analysis of groups of genes in high-throughput experiments. Nucleic Acids Res 33, W460–W464
    [Google Scholar]
  2. Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S. & other authors ( 2000; ). Gene ontology: tool for the unification of biology. Nat Genet 25, 25–29.[CrossRef]
    [Google Scholar]
  3. Baldi, P. & Long, A. D. ( 2001; ). A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 17, 509–519.[CrossRef]
    [Google Scholar]
  4. Banno, T., Gazel, A. & Blumenberg, M. ( 2005; ). Pathway-specific profiling identifies the NF-κB-dependent tumor necrosis factor α-regulated genes in epidermal keratinocytes. J Biol Chem 280, 18973–18980.[CrossRef]
    [Google Scholar]
  5. Boniotto, M., Jordan, W. J., Eskdale, J., Tossi, A., Antcheva, N., Crovella, S., Connell, N. D. & Gallagher, G. ( 2006; ). Human β-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob Agents Chemother 50, 1433–1441.[CrossRef]
    [Google Scholar]
  6. Chung, W. O. & Dale, B. A. ( 2004; ). Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Infect Immun 72, 352–358.[CrossRef]
    [Google Scholar]
  7. Chung, W. O., Hansen, S. R., Rao, D. & Dale, B. A. ( 2004; ). Protease-activated receptor signaling increases epithelial antimicrobial peptide expression. J Immunol 173, 5165–5170.[CrossRef]
    [Google Scholar]
  8. Collier-Hyams, L. S. & Neish, A. S. ( 2005; ). Innate immune relationship between commensal flora and the mammalian intestinal epithelium. Cell Mol Life Sci 62, 1339–1348.[CrossRef]
    [Google Scholar]
  9. Curtis, M. A., Aduse-Opoku, J. & Rangarajan, M. ( 2001; ). Cysteine proteases of Porphyromonas gingivalis. Crit Rev Oral Biol Med 12, 192–216.[CrossRef]
    [Google Scholar]
  10. Dale, B. A., Kimball, J. R., Krisanaprakornkit, S., Roberts, F., Robinovitch, M., O'Neal, R., Valore, E. V., Ganz, T., Anderson, G. M. & Weinberg, A. ( 2001; ). Localized antimicrobial peptide expression in human gingiva. J Periodontal Res 36, 285–294.[CrossRef]
    [Google Scholar]
  11. Darveau, R. P., Belton, C. M., Reife, R. A. & Lamont, R. J. ( 1998; ). Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infect Immun 66, 1660–1665.
    [Google Scholar]
  12. de Hoon, M. J., Imoto, S., Nolan, J. & Miyano, S. ( 2004; ). Open source clustering software. Bioinformatics 20, 1453–1454.[CrossRef]
    [Google Scholar]
  13. Doniger, S. W., Salomonis, N., Dahlquist, K. D., Vranizan, K., Lawlor, S. C. & Conklin, B. R. ( 2003; ). MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data. Genome Biol 4, R7 [CrossRef]
    [Google Scholar]
  14. Durr, M. & Peschel, A. ( 2002; ). Chemokines meet defensins: the merging concepts of chemoattractants and antimicrobial peptides in host defense. Infect Immun 70, 6515–6517.[CrossRef]
    [Google Scholar]
  15. Eisen, M. B., Spellman, P. T., Brown, P. O. & Botstein, D. ( 1998; ). Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95, 14863–14868.[CrossRef]
    [Google Scholar]
  16. Fan, J., Heller, N. M., Gorospe, M., Atasoy, U. & Stellato, C. ( 2005; ). The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy. Eur Respir J 26, 933–947.[CrossRef]
    [Google Scholar]
  17. Fenno, J. C., Lee, S. Y., Bayer, C. H. & Ning, Y. ( 2001; ). The opdB locus encodes the trypsin-like peptidase activity of Treponema denticola. Infect Immun 69, 6193–6200.[CrossRef]
    [Google Scholar]
  18. Ferran, C., Stroka, D. M., Badrichani, A. Z., Cooper, J. T., Wrighton, C. J., Soares, M., Grey, S. T. & Bach, F. H. ( 1998; ). A20 inhibits NF-κB activation in endothelial cells without sensitizing to tumor necrosis factor-mediated apoptosis. Blood 91, 2249–2258.
    [Google Scholar]
  19. Ganz, T. ( 2003; ). Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3, 710–720.[CrossRef]
    [Google Scholar]
  20. Gibbs, S., Fijneman, R., Wiegant, J., van Kessel, A. G., van De Putte, P. & Backendorf, C. ( 1993; ). Molecular characterization and evolution of the SPRR family of keratinocyte differentiation markers encoding small proline-rich proteins. Genomics 16, 630–637.[CrossRef]
    [Google Scholar]
  21. Gon, Y., Asai, Y., Hashimoto, S., Mizumura, K., Jibiki, I., Machino, T., Ra, C. & Horie, T. ( 2004; ). A20 inhibits Toll-like receptor 2- and 4-mediated interleukin-8 synthesis in airway epithelial cells. Am J Respir Cell Mol Biol 31, 330–336.[CrossRef]
    [Google Scholar]
  22. Greaves, D. R., Wang, W., Dairaghi, D. J., Dieu, M. C., Saint-Vis, B., Franz-Bacon, K., Rossi, D., Caux, C., McClanahan, T. & other authors ( 1997; ). CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3α and is highly expressed in human dendritic cells. J Exp Med 186, 837–844.[CrossRef]
    [Google Scholar]
  23. Handfield, M., Mans, J. J., Zheng, G., Lopez, M. C., Mao, S., Progulske-Fox, A., Narasimhan, G., Baker, H. V. & Lamont, R. J. ( 2005; ). Distinct transcriptional profiles characterize oral epithelium-microbiota interactions. Cell Microbiol 7, 811–823.[CrossRef]
    [Google Scholar]
  24. Harris, M. A., Clark, J., Ireland, A., Lomax, J., Ashburner, M., Foulger, R., Eilbeck, K., Lewis, S., Marshall, B. & other authors ( 2004; ). The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res 32, D258–D261.[CrossRef]
    [Google Scholar]
  25. Hasan, L., Mazzucchelli, L., Liebi, M., Lis, M., Hunger, R. E., Tester, A., Overall, C. M. & Wolf, M. ( 2006; ). Function of liver activation-regulated chemokine/CC chemokine ligand 20 is differently affected by cathepsin B and cathepsin D processing. J Immunol 176, 6512–6522.[CrossRef]
    [Google Scholar]
  26. Hasegawa, Y., Mans, J. J., Mao, S., Lopez, M. C., Baker, H. V., Handfield, M. & Lamont, R. J. ( 2007; ). Gingival epithelial cell transcriptional responses to commensal and opportunistic oral microbial species. Infect Immun 75, 2540–2547.[CrossRef]
    [Google Scholar]
  27. Holzhausen, M., Spolidorio, L. C. & Vergnolle, N. ( 2005; ). Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis. Mem Inst Oswaldo Cruz 100 (Suppl. 1), 177–180.
    [Google Scholar]
  28. Holzhausen, M., Spolidorio, L. C., Ellen, R. P., Jobin, M. C., 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.[CrossRef]
    [Google Scholar]
  29. Inano, H., Kameyama, S., Yasui, S. & Nagai, A. ( 1998; ). Granulocyte colony-stimulating factor induces neutrophil sequestration in rabbit lungs. Am J Respir Cell Mol Biol 19, 167–174.[CrossRef]
    [Google Scholar]
  30. Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J. L., Schroter, M., Burns, K. & other authors ( 1997; ). Inhibition of death receptor signals by cellular FLIP. Nature 388, 190–195.[CrossRef]
    [Google Scholar]
  31. Ismail, A. S. & Hooper, L. V. ( 2005; ). Epithelial cells and their neighbors. IV. Bacterial contributions to intestinal epithelial barrier integrity. Am J Physiol Gastrointest Liver Physiol 289, G779–G784.[CrossRef]
    [Google Scholar]
  32. Jonca, N., Guerrin, M., Hadjiolova, K., Caubet, C., Gallinaro, H., Simon, M. & Serre, G. ( 2002; ). Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties. J Biol Chem 277, 5024–5029.[CrossRef]
    [Google Scholar]
  33. Kelly, D., Campbell, J. I., King, T. P., Grant, G., Jansson, E. A., Coutts, A. G., Pettersson, S. & Conway, S. ( 2004; ). Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA. Nat Immunol 5, 104–112.[CrossRef]
    [Google Scholar]
  34. Kelly, D., Conway, S. & Aminov, R. ( 2005; ). Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol 26, 326–333.[CrossRef]
    [Google Scholar]
  35. Kinane, D. F., Shiba, H., Stathopoulou, P. G., Zhao, H., Lappin, D. F., Singh, A., Eskan, M. A., Beckers, S., Waigel, S. & other authors ( 2006; ). Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399Ile are hypo-responsive to Porphyromonas gingivalis. Genes Immun 7, 190–200.[CrossRef]
    [Google Scholar]
  36. Kolenbrander, P. E. ( 2000; ). Oral microbial communities: biofilms, interactions, and genetic systems. Annu Rev Microbiol 54, 413–437.[CrossRef]
    [Google Scholar]
  37. Kolenbrander, P. E., Andersen, R. N., Blehert, D. S., Egland, P. G., Foster, J. S. & Palmer, R. J., Jr ( 2002; ). Communication among oral bacteria. Microbiol Mol Biol Rev 66, 486–505.[CrossRef]
    [Google Scholar]
  38. Krisanaprakornkit, S., Weinberg, A., Perez, C. N. & Dale, B. A. ( 1998; ). Expression of the peptide antibiotic human β-defensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun 66, 4222–4228.
    [Google Scholar]
  39. Krisanaprakornkit, S., Kimball, J. R., Weinberg, A., Darveau, R. P., Bainbridge, B. W. & Dale, B. A. ( 2000; ). Inducible expression of human β-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect Immun 68, 2907–2915.[CrossRef]
    [Google Scholar]
  40. Krisanaprakornkit, S., Kimball, J. R. & Dale, B. A. ( 2002; ). Regulation of human β-defensin-2 in gingival epithelial cells: the involvement of mitogen-activated protein kinase pathways, but not the NF-κB transcription factor family. J Immunol 168, 316–324.[CrossRef]
    [Google Scholar]
  41. Lamont, R. J., Chan, A., Belton, C. M., Izutsu, K. T., Vasel, D. & Weinberg, A. ( 1995; ). Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun 63, 3878–3885.
    [Google Scholar]
  42. Liu, L., Wang, L., Jia, H. P., Zhao, C., Heng, H. H., Schutte, B. C., McCray, P. B., Jr & Ganz, T. ( 1998; ). Structure and mapping of the human β-defensin HBD-2 gene and its expression at sites of inflammation. Gene 222, 237–244.[CrossRef]
    [Google Scholar]
  43. Lourbakos, A., Potempa, J., Travis, J., D'Andrea, M. R., Andrade-Gordon, P., Santulli, R., Mackie, E. J. & Pike, R. N. ( 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.[CrossRef]
    [Google Scholar]
  44. Lu, Q., Jin, L., Darveau, R. P. & Samaranayake, L. P. ( 2004; ). Expression of human β-defensins-1 and -2 peptides in unresolved chronic periodontitis. J Periodontal Res 39, 221–227.[CrossRef]
    [Google Scholar]
  45. Macpherson, A. J. & Harris, N. L. ( 2004; ). Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4, 478–485.[CrossRef]
    [Google Scholar]
  46. Magert, H. J., Drogemuller, K. & Raghunath, M. ( 2005; ). Serine proteinase inhibitors in the skin: role in homeostasis and disease. Curr Protein Pept Sci 6, 241–254.[CrossRef]
    [Google Scholar]
  47. McMichael, J. W., Maxwell, A. I., Hayashi, K., Taylor, K., Wallace, W. A., Govan, J. R., Dorin, J. R. & Sallenave, J. M. ( 2005; ). Antimicrobial activity of murine lung cells against Staphylococcus aureus is increased in vitro and in vivo after elafin gene transfer. Infect Immun 73, 3609–3617.[CrossRef]
    [Google Scholar]
  48. Mizutani, H., Black, R. & Kupper, T. S. ( 1991; ). Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta. Different strategies of IL-1 production and processing in monocytes and keratinocytes. J Clin Invest 87, 1066–1071.[CrossRef]
    [Google Scholar]
  49. Mondino, A. & Blasi, F. ( 2004; ). uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol 25, 450–455.[CrossRef]
    [Google Scholar]
  50. Neish, A. S., Gewirtz, A. T., Zeng, H., Young, A. N., Hobert, M. E., Karmali, V., Rao, A. S. & Madara, J. L. ( 2000; ). Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination. Science 289, 1560–1563.[CrossRef]
    [Google Scholar]
  51. Niyonsaba, F., Ogawa, H. & Nagaoka, I. ( 2004; ). Human β-defensin-2 functions as a chemotactic agent for tumour necrosis factor-α-treated human neutrophils. Immunology 111, 273–281.[CrossRef]
    [Google Scholar]
  52. Niyonsaba, F., Ushio, H., Nagaoka, I., Okumura, K. & Ogawa, H. ( 2005; ). The human β-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, 1776–1784.[CrossRef]
    [Google Scholar]
  53. Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R. & other authors ( 2001; ). A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606.[CrossRef]
    [Google Scholar]
  54. Pfaffl, M. W. ( 2001; ). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29, e45 [CrossRef]
    [Google Scholar]
  55. Qin, J., Qian, Y., Yao, J., Grace, C. & Li, X. ( 2005; ). SIGIRR inhibits interleukin-1 receptor- and Toll-like receptor 4-mediated signaling through different mechanisms. J Biol Chem 280, 25233–25241.[CrossRef]
    [Google Scholar]
  56. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. ( 2004; ). Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118, 229–241.[CrossRef]
    [Google Scholar]
  57. Saeed, A. I., Sharov, V., White, J., Li, J., Liang, W., Bhagabati, N., Braisted, J., Klapa, M., Currier, T. & other authors ( 2003; ). TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34, 374–378.
    [Google Scholar]
  58. Saito, T., Ishihara, K., Kato, T. & Okuda, K. ( 1997; ). Cloning, expression, and sequencing of a protease gene from Bacteroides forsythus ATCC 43037 in Escherichia coli. Infect Immun 65, 4888–4891.
    [Google Scholar]
  59. Sallenave, J. M., Cunningham, G. A., James, R. M., McLachlan, G. & Haslett, C. ( 2003; ). Regulation of pulmonary and systemic bacterial lipopolysaccharide responses in transgenic mice expressing human elafin. Infect Immun 71, 3766–3774.[CrossRef]
    [Google Scholar]
  60. Sansonetti, P. J. ( 2004; ). War and peace at mucosal surfaces. Nat Rev Immunol 4, 953–964.[CrossRef]
    [Google Scholar]
  61. Socransky, S. S., Haffajee, A. D., Cugini, M. A., Smith, C. & Kent, R. L., Jr ( 1998; ). Microbial complexes in subgingival plaque. J Clin Periodontol 25, 134–144.[CrossRef]
    [Google Scholar]
  62. Strober, W., Murray, P. J., Kitani, A. & Watanabe, T. ( 2006; ). Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 6, 9–20.[CrossRef]
    [Google Scholar]
  63. Tien, M. T., Girardin, S. E., Regnault, B., Le Bourhis, L., Dillies, M. A., Coppee, J. Y., Bourdet-Sicard, R., Sansonetti, P. J. & Pedron, T. ( 2006; ). Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells. J Immunol 176, 1228–1237.[CrossRef]
    [Google Scholar]
  64. Tonetti, M. S., Imboden, M. A. & Lang, N. P. ( 1998; ). Neutrophil migration into the gingival sulcus is associated with transepithelial gradients of interleukin-8 and ICAM-1. J Periodontol 69, 1139–1147.[CrossRef]
    [Google Scholar]
  65. Uehara, A., Sugawara, S., Muramoto, K. & Takada, H. ( 2002; ). Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2. J Immunol 169, 4594–4603.[CrossRef]
    [Google Scholar]
  66. van der Reijden, W. A., Bosch-Tijhof, C. J., Strooker, H. & van Winkelhoff, A. J. ( 2006; ). prtH in Tannerella forsythensis is not associated with periodontitis. J Periodontol 77, 586–590.[CrossRef]
    [Google Scholar]
  67. Wald, D., Qin, J., Zhao, Z., Qian, Y., Naramura, M., Tian, L., Towne, J., Sims, J. E., Stark, G. R. & Li, X. ( 2003; ). SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 4, 920–927.[CrossRef]
    [Google Scholar]
  68. Wehkamp, J., Harder, J., Wehkamp, K., Wehkamp-von Meissner, B., Schlee, M., Enders, C., Sonnenborn, U., Nuding, S., Bengmark, S. & other authors ( 2004; ). NF-κB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect Immun 72, 5750–5758.[CrossRef]
    [Google Scholar]
  69. Wertz, I. E., O'Rourke, K. M., Zhou, H., Eby, M., Aravind, L., Seshagiri, S., Wu, P., Wiesmann, C., Baker, R. & other authors ( 2004; ). De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kB signalling. Nature 430, 694–699.[CrossRef]
    [Google Scholar]
  70. Whitney, A. R., Diehn, M., Popper, S. J., Alizadeh, A. A., Boldrick, J. C., Relman, D. A. & Brown, P. O. ( 2003; ). Individuality and variation in gene expression patterns in human blood. Proc Natl Acad Sci U S A 100, 1896–1901.[CrossRef]
    [Google Scholar]
  71. Wolach, B., Gavrieli, R. & Pomeranz, A. ( 2000; ). Effect of granulocyte and granulocyte macrophage colony stimulating factors (G-CSF and GM-CSF) on neonatal neutrophil functions. Pediatr Res 48, 369–373.[CrossRef]
    [Google Scholar]
  72. Wright, G. W. & Simon, R. M. ( 2003; ). A random variance model for detection of differential gene expression in small microarray experiments. Bioinformatics 19, 2448–2455.[CrossRef]
    [Google Scholar]
  73. Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schroder, J. M., Wang, J. M. & other authors ( 1999; ). β-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286, 525–528.[CrossRef]
    [Google Scholar]
  74. Yang, D., Biragyn, A., Hoover, D. M., Lubkowski, J. & Oppenheim, J. J. ( 2004; ). Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 22, 181–215.[CrossRef]
    [Google Scholar]
  75. Zhou, Q. & Amar, S. ( 2006; ). Identification of proteins differentially expressed in human monocytes exposed to Porphyromonas gingivalis and its purified components by high-throughput immunoblotting. Infect Immun 74, 1204–1214.[CrossRef]
    [Google Scholar]
  76. Zhu, J., Nathan, C., Jin, W., Sim, D., Ashcroft, G. S., Wahl, S. M., Lacomis, L., Erdjument-Bromage, H., Tempst, P. & other authors ( 2002; ). Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111, 867–878.[CrossRef]
    [Google Scholar]
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