DOI QR코드

DOI QR Code

Oxygen matters: hypoxia as a pathogenic mechanism in rhinosinusitis

  • Cho, Hyung-Ju (Department of Otorhinolaryngology, Yonsei University College of Medicine) ;
  • Kim, Chang-Hoon (Department of Otorhinolaryngology, Yonsei University College of Medicine)
  • Received : 2017.12.27
  • Published : 2018.02.28

Abstract

The airway epithelium is the first place, where a defense mechanism is initiated against environmental stimuli. Mucociliary transport (MCT), which is the defense mechanism of the airway and the role of airway epithelium as mechanical barriers are essential in innate immunity. To maintain normal physiologic function, normal oxygenation is critical for the production of energy for optimal cellular functions. Several pathologic conditions are associated with a decrease in oxygen tension in airway epithelium and chronic sinusitis is one of the airway diseases, which is associated with the hypoxic condition, a potent inflammatory stimulant. We have observed the overexpression of the hypoxia-inducible factor 1 (HIF-1), an essential factor for oxygen homeostasis, in the epithelium of sinus mucosa in sinusitis patients. In a series of previous reports, we have found hypoxia-induced mucus hyperproduction, especially by MUC5AC hyperproduction, disruption of epithelial barrier function by the production of VEGF, and down-regulation of junctional proteins such as ZO-1 and E-cadherin. Furthermore, hypoxia-induced inflammation by HMGB1 translocation into the cytoplasm results in the release of IL-8 through a ROS-dependent mechanism in upper airway epithelium. In this mini-review, we briefly introduce and summarize current progress in the pathogenesis of sinusitis related to hypoxia. The investigation of hypoxia-related pathophysiology in airway epithelium will suggest new insights on airway inflammatory diseases, such as rhinosinusitis for clinical application and drug development.

Keywords

Airway;Epithelial junction;Epithelium;$HIF-1{\alpha}$;Hypoxia;Innate immunity;Mucin;Rhinosinusitis;VEGF

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Zabner J, Winter M, Excoffon KJ et al (2003) Histamine alters E-cadherin cell adhesion to increase human airway epithelial permeability. J Appl Physiol 95, 394-401 https://doi.org/10.1152/japplphysiol.01134.2002
  2. Jain M and Sznajder JI (2005) Effects of hypoxia on the alveolar epithelium. Proc Am Thorac Soc 2, 202-205 https://doi.org/10.1513/pats.200501-006AC
  3. Bunn HF and Poyton RO (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev 76, 839-885 https://doi.org/10.1152/physrev.1996.76.3.839
  4. Steinke JW, Woodard CR and Borish L (2008) Role of hypoxia in inflammatory upper airway disease. Curr Opin Allergy Clin Immunol 8, 16-20 https://doi.org/10.1097/ACI.0b013e3282f3f488
  5. Lok CN and Ponka P (1999) Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem 274, 24147-24152 https://doi.org/10.1074/jbc.274.34.24147
  6. Matsune S, Kono M, Sun D, Ushikai M and Kurono Y (2003) Hypoxia in paranasal sinuses of patients with chronic sinusitis with or without the complication of nasal allergy. Acta Otolaryngol 123, 519-523 https://doi.org/10.1080/0036554021000028113
  7. Rose MC and Voynow JA (2006) Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 86, 245-278 https://doi.org/10.1152/physrev.00010.2005
  8. Semenza GL and Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12, 5447-5454 https://doi.org/10.1128/MCB.12.12.5447
  9. Levy AP, Levy NS, Wegner S and Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270, 13333-13340 https://doi.org/10.1074/jbc.270.22.13333
  10. Lee PJ, Jiang BH, Chin BY et al (1997) Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem 272, 5375-5381 https://doi.org/10.1074/jbc.272.9.5375
  11. Rolfs A, Kvietikova I, Gassmann M and Wenger RH (1997) Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1. J Biol Chem 272, 20055-20062 https://doi.org/10.1074/jbc.272.32.20055
  12. Wang GL and Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270, 1230-1237 https://doi.org/10.1074/jbc.270.3.1230
  13. Neruntarat C (2003) Uvulopalatal flap for snoring on an outpatient basis. Otolaryngol Head Neck Surg 129, 353-359 https://doi.org/10.1016/S0194-5998(03)00636-3
  14. Semenza GL (1998) Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. J Lab Clin Med 131, 207-214 https://doi.org/10.1016/S0022-2143(98)90091-9
  15. Semenza GL, Jiang BH, Leung SW et al (1996) Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271, 32529-32537 https://doi.org/10.1074/jbc.271.51.32529
  16. Forsythe JA, Jiang BH, Iyer NV et al (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16, 4604-4613 https://doi.org/10.1128/MCB.16.9.4604
  17. Li D, Gallup M, Fan N, Szymkowski DE and Basbaum CB (1998) Cloning of the amino-terminal and 5'-flanking region of the human MUC5AC mucin gene and transcriptional up-regulation by bacterial exoproducts. J Biol Chem 273, 6812-6820 https://doi.org/10.1074/jbc.273.12.6812
  18. Young HW, Williams OW, Chandra D et al (2007) Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5' elements. Am J Respir Cell Mol Biol 37, 273-290 https://doi.org/10.1165/rcmb.2005-0460OC
  19. Yoon JH, Moon HJ, Seong JK et al (2002) Mucociliary differentiation according to time in human nasal epithelial cell culture. Differentiation 70, 77-83 https://doi.org/10.1046/j.1432-0436.2002.700202.x
  20. Kim YJ, Cho HJ, Shin WC, Song HA, Yoon JH and Kim CH (2014) Hypoxia-Mediated Mechanism of MUC5AC Production in Human Nasal Epithelia and Its Implication in Rhinosinusitis. PLoS One 9, e98136 https://doi.org/10.1371/journal.pone.0098136
  21. Miyamoto N, de Kozak Y, Normand N et al (2008) PlGF-1 and VEGFR-1 pathway regulation of the external epithelial hemato-ocular barrier. A model for retinal edema. Ophthalmic Res 40, 203-207 https://doi.org/10.1159/000119877
  22. Ahdieh M, Vandenbos T and Youakim A (2001) Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma. Am J Physiol Cell Physiol 281, C2029-2038 https://doi.org/10.1152/ajpcell.2001.281.6.C2029
  23. Sajjan U, Wang Q, Zhao Y, Gruenert DC and Hershenson MB (2008) Rhinovirus disrupts the barrier function of polarized airway epithelial cells. Am J Respir Crit Care Med 178, 1271-1281 https://doi.org/10.1164/rccm.200801-136OC
  24. Weis SM and Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437, 497-504 https://doi.org/10.1038/nature03987
  25. Aiello LP, Avery RL, Arrigg PG et al (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331, 1480-1487 https://doi.org/10.1056/NEJM199412013312203
  26. Nagashima M, Yoshino S, Ishiwata T and Asano G (1995) Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis. J Rheumatol 22, 1624-1630
  27. Jung HH, Kim MW, Lee JH et al (1999) Expression of vascular endothelial growth factor in otitis media. Acta Otolaryngol 119, 801-808 https://doi.org/10.1080/00016489950180450
  28. Matsune S, Ohori J, Sun D, Yoshifuku K, Fukuiwa T and Kurono Y (2008) Vascular endothelial growth factor produced in nasal glands of perennial allergic rhinitis. Am J Rhinol 22, 365-370 https://doi.org/10.2500/ajr.2008.22.3190
  29. Lee YC, Kwak YG and Song CH (2002) Contribution of vascular endothelial growth factor to airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma. J Immunol 168, 3595-3600 https://doi.org/10.4049/jimmunol.168.7.3595
  30. Sun D, Matsune S, Ohori J, Fukuiwa T, Ushikai M and Kurono Y (2005) TNF-alpha and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion. Auris Nasus Larynx 32, 243-249 https://doi.org/10.1016/j.anl.2005.01.004
  31. Divekar RD, Samant S, Rank MA et al (2015) Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GM-CSF signatures during symptomatic exacerbations. Clin Exp Allergy 45, 767-778 https://doi.org/10.1111/cea.12463
  32. Song HA, Kim YS, Cho HJ et al (2017) Hypoxia Modulates Epithelial Permeability via Regulation of Vascular Endothelial Growth Factor in Airway Epithelia. Am J Respir Cell Mol Biol 57, 527-535 https://doi.org/10.1165/rcmb.2016-0080OC
  33. Takano K, Kojima T, Go M et al (2005) HLA-DR- and CD11c-positive dendritic cells penetrate beyond well-developed epithelial tight junctions in human nasal mucosa of allergic rhinitis. J Histochem Cytochem 53, 611-619 https://doi.org/10.1369/jhc.4A6539.2005
  34. Nelson WJ (2003) Adaptation of core mechanisms to generate cell polarity. Nature 422, 766-774 https://doi.org/10.1038/nature01602
  35. Niessen CM (2007) Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 127, 2525-2532 https://doi.org/10.1038/sj.jid.5700865
  36. Capaldo CT and Macara IG (2007) Depletion of E-cadherin disrupts establishment but not maintenance of cell junctions in Madin-Darby canine kidney epithelial cells. Mol Biol Cell 18, 189-200
  37. Takeuchi K, Kishioka C, Ishinaga H, Sakakura Y and Majima Y (2001) Histamine alters gene expression in cultured human nasal epithelial cells. J Allergy Clin Immunol 107, 310-314 https://doi.org/10.1067/mai.2001.112127
  38. Jang YJ, Kim HG, Koo TW and Chung PS (2002) Localization of ZO-1 and E-cadherin in the nasal polyp epithelium. Eur Arch Otorhinolaryngol 259, 465-469
  39. Yeo NK and Jang YJ (2010) Rhinovirus infection-induced alteration of tight junction and adherens junction components in human nasal epithelial cells. Laryngoscope 120, 346-352
  40. Min HJ, Kim TH, Yoon JH and Kim CH (2015) Hypoxia increases epithelial permeability in human nasal epithelia. Yonsei Med J 56, 825-831 https://doi.org/10.3349/ymj.2015.56.3.825
  41. Lotze MT and Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5, 331-342 https://doi.org/10.1038/nri1594
  42. Bonaldi T, Talamo F, Scaffidi P et al (2003) Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22, 5551-5560 https://doi.org/10.1093/emboj/cdg516
  43. Hori O, Brett J, Slattery T et al (1995) The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem 270, 25752-25761 https://doi.org/10.1074/jbc.270.43.25752
  44. Tang D, Kang R, Livesey KM et al (2010) Endogenous HMGB1 regulates autophagy. J Cell Biol 190, 881-892 https://doi.org/10.1083/jcb.200911078
  45. Han SJ, Min HJ, Yoon SC et al (2015) HMGB1 in the pathogenesis of ultraviolet-induced ocular surface inflammation. Cell Death Dis 6, e1863 https://doi.org/10.1038/cddis.2015.199
  46. Min HJ, Kim SJ, Kim TH, Chung HJ, Yoon JH and Kim CH (2015) Level of secreted HMGB1 correlates with severity of inflammation in chronic rhinosinusitis. Laryngoscope 125, E225-230 https://doi.org/10.1002/lary.25172
  47. Itoh T, Iwahashi S, Shimoda M et al (2011) High-mobility group box 1 expressions in hypoxia-induced damaged mouse islets. Transplant Proc 43, 3156-3160 https://doi.org/10.1016/j.transproceed.2011.09.100
  48. Hamada T, Torikai M, Kuwazuru A et al (2008) Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum 58, 2675-2685 https://doi.org/10.1002/art.23729
  49. Min HJ, Kim JH, Yoo JE et al (2017) ROS-dependent HMGB1 secretion upregulates IL-8 in upper airway epithelial cells under hypoxic condition. Mucosal Immunol 10, 685-694 https://doi.org/10.1038/mi.2016.82
  50. Desireddi JR, Farrow KN, Marks JD, Waypa GB and Schumacker PT (2010) Hypoxia increases ROS signaling and cytosolic Ca(2+) in pulmonary artery smooth muscle cells of mouse lungs slices. Antioxid Redox Signal 12, 595-602 https://doi.org/10.1089/ars.2009.2862
  51. Joo JH, Ryu JH, Kim CH et al (2012) Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa. Antioxid Redox Signal 16, 57-70 https://doi.org/10.1089/ars.2011.3898
  52. Riechelmann H, Deutschle T, Friemel E, Gross HJ and Bachem M (2003) Biological markers in nasal secretions. Eur Respir J 21, 600-605 https://doi.org/10.1183/09031936.03.00072003
  53. Riechelmann H, Deutschle T, Rozsasi A, Keck T, Polzehl D and Burner H (2005) Nasal biomarker profiles in acute and chronic rhinosinusitis. Clin Exp Allergy 35, 1186-1191 https://doi.org/10.1111/j.1365-2222.2005.02316.x
  54. Kramer MF, Burow G, Pfrogner E and Rasp G (2004) In vitro diagnosis of chronic nasal inflammation. Clin Exp Allergy 34, 1086-1092 https://doi.org/10.1111/j.1365-2222.2004.01989.x
  55. Deroee AF, Naraghi M, Sontou AF, Ebrahimkhani MR and Dehpour AR (2009) Nitric oxide metabolites as biomarkers for follow-up after chronic rhinosinusitis surgery. Am J Rhinol Allergy 23, 159-161 https://doi.org/10.2500/ajra.2009.23.3289
  56. Shimizu S, Kouzaki H, Kato T, Tojima I and Shimizu T (2016) HMGB1-TLR4 signaling contributes to the secretion of interleukin 6 and interleukin 8 by nasal epithelial cells. Am J Rhinol Allergy 30, 167-172 https://doi.org/10.2500/ajra.2016.30.4300
  57. Paris G, Pozharskaya T, Asempa T and Lane AP (2014) Damage-associated molecular patterns stimulate interleukin-33 expression in nasal polyp epithelial cells. Int Forum Allergy Rhinol 4, 15-21 https://doi.org/10.1002/alr.21237
  58. Yang H, Wang H, Czura CJ and Tracey KJ (2005) The cytokine activity of HMGB1. J Leukoc Biol 78, 1-8 https://doi.org/10.1189/jlb.1104648
  59. Lv B, Wang H, Tang Y, Fan Z, Xiao X and Chen F (2009) High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-kappaB and Egr-1. Thromb Haemost 102, 352-359 https://doi.org/10.1160/TH08-11-0759
  60. Fiuza C, Bustin M, Talwar S et al (2003) Inflammationpromoting activity of HMGB1 on human microvascular endothelial cells. Blood 101, 2652-2660 https://doi.org/10.1182/blood-2002-05-1300