The Unfolded Protein Response in Cystic Fibrosis: Comparison
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Please note this is a comparison between Version 2 by Nora Tang and Version 1 by Pascal Trouvé.

The UPR is responsible for the activation of degradation genes of the ERAD, the increased expression of chaperons and limits the global protein synthesis in cells. It limits the expression of the p.Phe508del-CFTR itself, by the activation of ATF6. Therefore, the hypothesis that it is likely triggered but becomes obvious when other events happen, including infection and/or inflammation, that also contribute the UPR triggering.

  • cystic fibrosis
  • unfolded protein response
  • inflammation
  • infection
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References

  1. Riordan, J.R.; Rommens, J.M.; Kerem, B.; Alon, N.; Rozmahel, R.; Grzelczak, Z.; Zielenski, J.; Lok, S.; Plavsic, N.; Chou, J.L. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 1989, 245, 1066–1073.
  2. Rich, D.P.; Anderson, M.P.; Gregory, R.J.; Cheng, S.H.; Paul, S.; Jefferson, D.M.; McCann, J.D.; Klinger, K.W.; Smith, A.E.; Welsh, M.J. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature 1990, 347, 358–363.
  3. Anderson, M.P.; Gregory, R.J.; Thompson, S.; Souza, D.W.; Paul, S.; Mulligan, R.C.; Smith, A.E.; Welsh, M.J. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 1991, 253, 202–205.
  4. Berdiev, B.K.; Qadri, Y.J.; Benos, D.J. Assessment of the CFTR and ENaC association. Mol. Biosyst. 2009, 5, 123–127.
  5. Heeckeren, A.; Walenga, R.; Konstan, M.W.; Bonfield, T.; Davis, P.B.; Ferkol, T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas Aeruginosa. J. Clin. Investig. 1997, 100, 2810–2815.
  6. Pier, G.B.; Grout, M.; Zaidi, T.S.; Olsen, J.C.; Johnson, L.G.; Yankaskas, J.R.; Goldberg, J.B. Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science 1996, 271, 64–67.
  7. Cheng, S.H.; Gregory, R.J.; Marshall, J.; Paul, S.; Souza, D.W.; White, G.A.; O’Riordan, C.R.; Smith, A.E. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 1990, 63, 827–834.
  8. Liu, C.Y.; Kaufman, R.J. The unfolded protein response. J. Cell Sci. 2003, 116 Pt 10, 1861–1862.
  9. Kaufman, R.J. Stress signaling from the lumen of the endoplasmic reticulum: Coordination of gene transcriptional and translational controls. Genes Dev. 1999, 13, 1211–1233.
  10. Schröder, M.; Kaufman, R.J. The mammalian unfolded protein response. Annu. Rev. Biochem. 2005, 74, 739–789.
  11. Ribeiro, C.M.P.; Boucher, R.C. Role of endoplasmic reticulum stress in cystic fibrosis-related airway inflammatory responses. Proc. Am. Thorac. Soc. 2010, 7, 387–394.
  12. Van’t Wout, E.F.A.; van Schadewijk, A.; van Boxtel, R.; Dalton, L.E.; Clarke, H.J.; Tommassen, J.; Marciniak, S.J.; Hiemstra, P.S. Virulence factors of Pseudomonas Aeruginosa induce both the unfolded protein and integrated stress responses in airway epithelial cells. PLoS Pathog. 2015, 11, e1004946.
  13. Nanua, S.; Sajjan, U.; Keshavjee, S.; Hershenson, M.B. Absence of typical unfolded protein response in primary cultured cystic fibrosis airway epithelial cells. Biochem. Biophys. Res. Commun. 2006, 343, 135–143.
  14. Kerbiriou, M.; Le Drévo, M.-A.; Férec, C.; Trouvé, P. Coupling cystic fibrosis to endoplasmic reticulum stress: Differential role of Grp78 and ATF6. Biochim. Biophys. Acta 2007, 1772, 1236–1249.
  15. Rab, A.; Bartoszewski, R.; Jurkuvenaite, A.; Wakefield, J.; Collawn, J.F.; Bebok, Z. Endoplasmic reticulum stress and the unfolded protein response regulate genomic cystic fibrosis transmembrane conductance regulator expression. Am. J. Physiol. Cell Physiol. 2007, 292, C756–C766.
  16. Bartoszewski, R.; Rab, A.; Jurkuvenaite, A.; Mazur, M.; Wakefield, J.; Collawn, J.F.; Bebok, Z. Activation of the unfolded protein response by DeltaF508 CFTR. Am. J. Respir. Cell Mol. Biol. 2008, 39, 448–457.
  17. Hull-Ryde, E.A.; Minges, J.T.; Martino, M.E.B.; Kato, T.; Norris-Drouin, J.L.; Ribeiro, C.M.P. IRE1α is a therapeutic target for cystic fibrosis airway inflammation. Int. J. Mol. Sci. 2021, 22, 3063.
  18. Ribeiro, C.M.P.; Lubamba, B.A. Role of IRE1α/XBP-1 in cystic fibrosis airway inflammation. Int. J. Mol. Sci. 2017, 18, E118.
  19. Bakunts, A.; Orsi, A.; Vitale, M.; Cattaneo, A.; Lari, F.; Tadè, L.; Sitia, R.; Raimondi, A.; Bachi, A.; van Anken, E. Ratiometric sensing of BiP-client versus BiP levels by the unfolded protein response determines its signaling amplitude. eLife 2017, 6, e27518.
  20. Vitale, M.; Bakunts, A.; Orsi, A.; Lari, F.; Tadè, L.; Danieli, A.; Rato, C.; Valetti, C.; Sitia, R.; Raimondi, A.; et al. Inadequate BiP availability defines endoplasmic reticulum stress. eLife 2019, 8, e41168.
  21. Blohmke, C.J.; Mayer, M.L.; Tang, A.C.; Hirschfeld, A.F.; Fjell, C.D.; Sze, M.A.; Falsafi, R.; Wang, S.; Hsu, K.; Chilvers, M.A.; et al. Atypical activation of the unfolded protein response in cystic fibrosis airway cells contributes to P38 MAPK-mediated innate immune responses. J. Immunol. 2012, 189, 5467–5475.
  22. Dobson, C.M. Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol. 2004, 15, 3–16.
  23. Karplus, M.; Weaver, D.L. Protein-folding dynamics. Nature 1976, 260, 404–406.
  24. Ohgushi, M.; Wada, A. “Molten-Globule State”: A compact form of globular proteins with mobile side-chains. FEBS Lett. 1983, 164, 21–24.
  25. Thomas, P.J.; Ko, Y.H.; Pedersen, P.L. Altered protein folding may be the molecular basis of most cases of cystic fibrosis. FEBS Lett. 1992, 312, 7–9.
  26. Bychkova, V.E.; Ptitsyn, O.B. Folding intermediates are involved in genetic diseases? FEBS Lett. 1995, 359, 6–8.
  27. Drumm, M.L.; Wilkinson, D.J.; Smit, L.S.; Worrell, R.T.; Strong, T.V.; Frizzell, R.A.; Dawson, D.C.; Collins, F.S. Chloride conductance expressed by Delta F508 and other mutant CFTRs in Xenopus Oocytes. Science 1991, 254, 1797–1799.
  28. Dalemans, W.; Barbry, P.; Champigny, G.; Jallat, S.; Dott, K.; Dreyer, D.; Crystal, R.G.; Pavirani, A.; Lecocq, J.P.; Lazdunski, M. Altered chloride ion channel kinetics associated with the Delta F508 cystic fibrosis mutation. Nature 1991, 354, 526–528.
  29. Choi, M.Y.; Partridge, A.W.; Daniels, C.; Du, K.; Lukacs, G.L.; Deber, C.M. Destabilization of the transmembrane domain induces misfolding in a phenotypic mutant of cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 2005, 280, 4968–4974.
  30. Ward, C.L.; Kopito, R.R. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J. Biol. Chem. 1994, 269, 25710–25718.
  31. Gottesman, S.; Wickner, S.; Maurizi, M.R. Protein quality control: Triage by chaperones and proteases. Genes Dev. 1997, 11, 815–823.
  32. Pind, S.; Riordan, J.R.; Williams, D.B. Participation of the endoplasmic reticulum chaperone calnexin (P88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 1994, 269, 12784–12788.
  33. Harada, K.; Okiyoneda, T.; Hashimoto, Y.; Ueno, K.; Nakamura, K.; Yamahira, K.; Sugahara, T.; Shuto, T.; Wada, I.; Suico, M.A.; et al. Calreticulin negatively regulates the cell surface expression of cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 2006, 281, 12841–12848.
  34. Knittler, M.R.; Dirks, S.; Haas, I.G. Molecular chaperones involved in protein degradation in the endoplasmic reticulum: Quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA 1995, 92, 1764–1768.
  35. McCracken, A.A.; Brodsky, J.L. Recognition and delivery of ERAD substrates to the proteasome and alternative paths for cell survival. Curr. Top. Microbiol. Immunol. 2005, 300, 17–40.
  36. El Khouri, E.; Le Pavec, G.; Toledano, M.B.; Delaunay-Moisan, A. RNF185 is a novel E3 ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). J. Biol. Chem. 2013, 288, 31177–31191.
  37. Rubenstein, R.C.; Zeitlin, P.L. Sodium 4-phenylbutyrate Downregulates Hsc70: Implications for Intracellular Trafficking of DeltaF508-CFTR. Available online: https://pubmed.ncbi.nlm.nih.gov/10666020/ (accessed on 21 August 2020).
  38. Meacham, G.C.; Lu, Z.; King, S.; Sorscher, E.; Tousson, A.; Cyr, D.M. The Hdj-2/Hsc70 Chaperone pair facilitates early steps in CFTR biogenesis. EMBO J. 1999, 18, 1492–1505.
  39. Zhang, Y.; Nijbroek, G.; Sullivan, M.L.; McCracken, A.A.; Watkins, S.C.; Michaelis, S.; Brodsky, J.L. Hsp70 molecular Chaperone facilitates endoplasmic reticulum-associated protein degradation of cystic fibrosis transmembrane conductance regulator in yeast. Mol. Biol. Cell 2001, 12, 1303–1314.
  40. Fu, L.; Rab, A.; Tang, L.P.; Bebok, Z.; Rowe, S.M.; Bartoszewski, R.; Collawn, J.F. ΔF508 CFTR surface stability is regulated by DAB2 and CHIP-mediated ubiquitination in post-endocytic compartments. PLoS ONE 2015, 10, e0123131.
  41. Ron, D.; Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 2007, 8, 519–529.
  42. Bertolotti, A.; Zhang, Y.; Hendershot, L.M.; Harding, H.P.; Ron, D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2000, 2, 326–332.
  43. Gething, M.J.; Sambrook, J. Protein folding in the cell. Nature 1992, 355, 33–45.
  44. Pobre, K.F.R.; Poet, G.J.; Hendershot, L.M. The endoplasmic reticulum (ER) Chaperone BiP is a master regulator of ER functions: Getting by with a little help from ERdj friends. J. Biol. Chem. 2019, 294, 2098–2108.
  45. Ting, J.; Lee, A.S. Human Gene Encoding the 78,000-Dalton Glucose-Regulated Protein and Its Pseudogene: Structure, Conservation, and Regulation; DNA Mary Ann Liebert Inc.: Larchmont, NY, USA, 1988; Volume 7, pp. 275–286.
  46. Melnyk, A.; Rieger, H.; Zimmermann, R. Co-Chaperones of the mammalian endoplasmic reticulum. Subcell. Biochem. 2015, 78, 179–200.
  47. Preissler, S.; Rato, C.; Chen, R.; Antrobus, R.; Ding, S.; Fearnley, I.M.; Ron, D. AMPylation matches BiP activity to client protein load in the endoplasmic reticulum. eLife 2015, 4, e12621.
  48. Gopal, U.; Pizzo, S.V. Cell surface GRP78 signaling: An emerging role as a transcriptional modulator in cancer. J. Cell. Physiol. 2021, 236, 2352–2363.
  49. Okada, T.; Haze, K.; Nadanaka, S.; Yoshida, H.; Seidah, N.G.; Hirano, Y.; Sato, R.; Negishi, M.; Mori, K. A Serine Protease Inhibitor Prevents Endoplasmic Reticulum Stress-Induced Cleavage but Not Transport of the Membrane-Bound Transcription Factor ATF6. Available online: https://pubmed.ncbi.nlm.nih.gov/12782636/ (accessed on 15 October 2021).
  50. Shen, J.; Chen, X.; Hendershot, L.; Prywes, R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of golgi localization signals. Dev. Cell 2002, 3, 99–111.
  51. Ye, J.; Rawson, R.B.; Komuro, R.; Chen, X.; Davé, U.P.; Prywes, R.; Brown, M.S.; Goldstein, J.L. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 2000, 6, 1355–1364.
  52. Hai, T.W.; Liu, F.; Coukos, W.J.; Green, M.R. Transcription factor ATF CDNA clones: An extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989, 3, 2083–2090.
  53. Yang, H.; Niemeijer, M.; van de Water, B.; Beltman, J.B. ATF6 is a critical determinant of CHOP dynamics during the unfolded protein response. iScience 2020, 23, 100860.
  54. Roy, B.; Lee, A.S. The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex. Nucleic Acids Res. 1999, 27, 1437–1443.
  55. Yoshida, H.; Haze, K.; Yanagi, H.; Yura, T.; Mori, K. Identification of the Cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. J. Biol. Chem. 1998, 273, 33741–33749.
  56. Haze, K.; Okada, T.; Yoshida, H.; Yanagi, H.; Yura, T.; Negishi, M.; Mori, K. Identification of the G13 (CAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response. Biochem. J. 2001, 355 Pt 1, 19–28.
  57. Thuerauf, D.J.; Marcinko, M.; Belmont, P.J.; Glembotski, C.C. Effects of the isoform-specific characteristics of ATF6 alpha and ATF6 beta on endoplasmic reticulum stress response gene expression and cell viability. J. Biol. Chem. 2007, 282, 22865–22878.
  58. Asada, R.; Kanemoto, S.; Kondo, S.; Saito, A.; Imaizumi, K. The signalling from endoplasmic reticulum-resident BZIP transcription factors involved in diverse cellular physiology. J. Biochem. 2011, 149, 507–518.
  59. Iwawaki, T.; Hosoda, A.; Okuda, T.; Kamigori, Y.; Nomura-Furuwatari, C.; Kimata, Y.; Tsuru, A.; Kohno, K. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat. Cell Biol. 2001, 3, 158–164.
  60. Martino, M.B.; Jones, L.; Brighton, B.; Ehre, C.; Abdulah, L.; Davis, C.W.; Ron, D.; O’Neal, W.K.; Ribeiro, C.M.P. The ER stress transducer IRE1β is required for airway epithelial mucin production. Mucosal Immunol. 2013, 6, 639–654.
  61. Ali, M.M.U.; Bagratuni, T.; Davenport, E.L.; Nowak, P.R.; Silva-Santisteban, M.C.; Hardcastle, A.; McAndrews, C.; Rowlands, M.G.; Morgan, G.J.; Aherne, W.; et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011, 30, 894–905.
  62. Sanches, M.; Duffy, N.M.; Talukdar, M.; Thevakumaran, N.; Chiovitti, D.; Canny, M.D.; Lee, K.; Kurinov, I.; Uehling, D.; Al-awar, R.; et al. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat. Commun. 2014, 5, 4202.
  63. Urano, F.; Wang, X.; Bertolotti, A.; Zhang, Y.; Chung, P.; Harding, H.P.; Ron, D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000, 287, 664–666.
  64. Sidrauski, C.; Walter, P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates MRNA splicing in the unfolded protein response. Cell 1997, 90, 1031–1039.
  65. Yoshida, H.; Matsui, T.; Yamamoto, A.; Okada, T.; Mori, K. XBP1 MRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001, 107, 881–891.
  66. Travers, K.J.; Patil, C.K.; Wodicka, L.; Lockhart, D.J.; Weissman, J.S.; Walter, P. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 2000, 101, 249–258.
  67. Iwakoshi, N.N.; Lee, A.-H.; Glimcher, L.H. The X-box binding protein-1 transcription factor is required for plasma cell differentiation and the unfolded protein response. Immunol. Rev. 2003, 194, 29–38.
  68. Sriburi, R.; Jackowski, S.; Mori, K.; Brewer, J.W. XBP1: A link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum. J. Cell Biol. 2004, 167, 35–41.
  69. So, J.-S.; Hur, K.Y.; Tarrio, M.; Ruda, V.; Frank-Kamenetsky, M.; Fitzgerald, K.; Koteliansky, V.; Lichtman, A.H.; Iwawaki, T.; Glimcher, L.H.; et al. Silencing of lipid metabolism genes through IRE1α-mediated MRNA decay lowers plasma lipids in mice. Cell Metab. 2012, 16, 487–499.
  70. Zhou, Y.; Lee, J.; Reno, C.M.; Sun, C.; Park, S.W.; Chung, J.; Lee, J.; Fisher, S.J.; White, M.F.; Biddinger, S.B.; et al. Regulation of Glucose Homeostasis through a XBP-1-FoxO1 Interaction. Nat. Med. 2011, 17, 356–365.
  71. Tao, R.; Chen, H.; Gao, C.; Xue, P.; Yang, F.; Han, J.-D.J.; Zhou, B.; Chen, Y.-G. Xbp1-mediated histone H4 deacetylation contributes to DNA double-strand break repair in yeast. Cell Res. 2011, 21, 1619–1633.
  72. Tirasophon, W.; Lee, K.; Callaghan, B.; Welihinda, A.; Kaufman, R.J. The endoribonuclease activity of mammalian IRE1 autoregulates its MRNA and is required for the unfolded protein response. Genes Dev. 2000, 14, 2725–2736.
  73. Maurel, M.; Chevet, E.; Tavernier, J.; Gerlo, S. Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem. Sci. 2014, 39, 245–254.
  74. Imagawa, Y.; Hosoda, A.; Sasaka, S.-I.; Tsuru, A.; Kohno, K. RNase domains determine the functional difference between IRE1alpha and IRE1beta. FEBS Lett. 2008, 582, 656–660.
  75. Shi, Y.; Vattem, K.M.; Sood, R.; An, J.; Liang, J.; Stramm, L.; Wek, R.C. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. Mol. Cell. Biol. 1998, 18, 7499–7509.
  76. McQuiston, A.; Diehl, J.A. Recent insights into PERK-dependent signaling from the stressed endoplasmic reticulum. F1000Research 2017, 6, 1897.
  77. Lloyd, M.A.; Osborne, J.C.; Safer, B.; Powell, G.M.; Merrick, W.C. Characteristics of eukaryotic initiation factor 2 and its subunits. J. Biol. Chem. 1980, 255, 1189–1193.
  78. Ernst, H.; Duncan, R.F.; Hershey, J.W. Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor EIF-2. characterization of the protein and its messenger RNA. J. Biol. Chem. 1987, 262, 1206–1212.
  79. Adams, S.L.; Safer, B.; Anderson, W.F.; Merrick, W.C. Eukaryotic initiation complex formation. Evidence for two distinct pathways. J. Biol. Chem. 1975, 250, 9083–9089.
  80. Rowlands, A.G.; Panniers, R.; Henshaw, E.C. The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2. J. Biol. Chem. 1988, 263, 5526–5533.
  81. Harding, H.P.; Zhang, Y.; Bertolotti, A.; Zeng, H.; Ron, D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 2000, 5, 897–904.
  82. Harding, H.P.; Novoa, I.; Zhang, Y.; Zeng, H.; Wek, R.; Schapira, M.; Ron, D. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol. Cell 2000, 6, 1099–1108.
  83. Vallejo, M.; Ron, D.; Miller, C.P.; Habener, J.F. C/ATF, a member of the activating transcription factor family of DNA-binding proteins, dimerizes with CAAT/enhancer-binding proteins and directs their binding to CAMP response elements. Proc. Natl. Acad. Sci. USA 1993, 90, 4679–4683.
  84. Palam, L.R.; Baird, T.D.; Wek, R.C. Phosphorylation of EIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation. J. Biol. Chem. 2011, 286, 10939–10949.
  85. McMahon, M.; Samali, A.; Chevet, E. Regulation of the unfolded protein response by noncoding RNA. Am. J. Physiol. Cell Physiol. 2017, 313, C243–C254.
  86. Bartoszewska, S.; Kochan, K.; Madanecki, P.; Piotrowski, A.; Ochocka, R.; Collawn, J.F.; Bartoszewski, R. Regulation of the unfolded protein response by MicroRNAs. Cell. Mol. Biol. Lett. 2013, 18, 555–578.
  87. Bisognin, A.; Sales, G.; Coppe, A.; Bortoluzzi, S.; Romualdi, C. MAGIA2: From MiRNA and genes expression data integrative analysis to MicroRNA-transcription factor mixed regulatory circuits (2012 Update). Nucleic Acids Res. 2012, 40, W13–W21.
  88. Bartoszewski, R.; Brewer, J.W.; Rab, A.; Crossman, D.K.; Bartoszewska, S.; Kapoor, N.; Fuller, C.; Collawn, J.F.; Bebok, Z. The unfolded protein response (UPR)-activated transcription factor X-box-binding protein 1 (XBP1) induces MicroRNA-346 expression that targets the human antigen peptide transporter 1 (TAP1) MRNA and governs immune regulatory genes. J. Biol. Chem. 2011, 286, 41862–41870.
  89. Gebert, M.; Bartoszewska, S.; Janaszak-Jasiecka, A.; Moszyńska, A.; Cabaj, A.; Króliczewski, J.; Madanecki, P.; Ochocka, R.J.; Crossman, D.K.; Collawn, J.F.; et al. PIWI proteins contribute to apoptosis during the UPR in human airway epithelial cells. Sci. Rep. 2018, 8, 16431.
  90. Iwasaki, Y.W.; Siomi, M.C.; Siomi, H. PIWI-Interacting RNA: Its biogenesis and functions. Annu. Rev. Biochem. 2015, 84, 405–433.
  91. Feghali, C.A.; Wright, T.M. Cytokines in acute and chronic inflammation. Front. Biosci. J. Virtual Libr. 1997, 2, d12–d26.
  92. Pillarisetti, N.; Williamson, E.; Linnane, B.; Skoric, B.; Robertson, C.F.; Robinson, P.; Massie, J.; Hall, G.L.; Sly, P.; Stick, S.; et al. Infection, inflammation, and lung function decline in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 2011, 184, 75–81.
  93. Ranganathan, S.C.; Parsons, F.; Gangell, C.; Brennan, S.; Stick, S.M.; Sly, P.D.; Australian Respiratory Early Surveillance Team for Cystic Fibrosis. Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis. Thorax 2011, 66, 408–413.
  94. Grommes, J.; Soehnlein, O. Contribution of neutrophils to acute lung injury. Mol. Med. Camb. Mass 2011, 17, 293–307.
  95. Lee, I.-T.; Yang, C.-M. Inflammatory signalings involved in airway and pulmonary diseases. Mediat. Inflamm. 2013, 2013, 791231.
  96. Aghasafari, P.; George, U.; Pidaparti, R. A Review of inflammatory mechanism in airway diseases. Inflamm. Res. Off. J. Eur. Histamine Res. Soc. AI 2019, 68, 59–74.
  97. Bonfield, T.L.; Panuska, J.R.; Konstan, M.W.; Hilliard, K.A.; Hilliard, J.B.; Ghnaim, H.; Berger, M. Inflammatory cytokines in cystic fibrosis lungs. Am. J. Respir. Crit. Care Med. 1995, 152 Pt 1, 2111–2118.
  98. Bonfield, T.L.; Konstan, M.W.; Berger, M. Altered respiratory epithelial cell cytokine production in cystic fibrosis. J. Allergy Clin. Immunol. 1999, 104, 72–78.
  99. Nichols, D.P.; Chmiel, J.F. Inflammation and its genesis in cystic fibrosis. Pediatr. Pulmonol. 2015, 50 (Suppl. 40), S39–S56.
  100. Bardin, P.; Sonneville, F.; Corvol, H.; Tabary, O. Emerging MicroRNA therapeutic approaches for cystic fibrosis. Front. Pharmacol. 2018, 9, 1113.
  101. Bardin, P.; Marchal-Duval, E.; Sonneville, F.; Blouquit-Laye, S.; Rousselet, N.; Le Rouzic, P.; Corvol, H.; Tabary, O. Small RNA and transcriptome sequencing reveal the role of MiR-199a-3p in inflammatory processes in cystic fibrosis airways. J. Pathol. 2018, 245, 410–420.
  102. White, N.M.; Jiang, D.; Burgess, J.D.; Bederman, I.R.; Previs, S.F.; Kelley, T.J. Altered cholesterol homeostasis in cultured and in vivo models of cystic fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007, 292, L476–L486.
  103. Brennan, S.; Sly, P.D.; Gangell, C.L.; Sturges, N.; Winfield, K.; Wikstrom, M.; Gard, S.; Upham, J.W.; AREST, C.F. Alveolar macrophages and CC chemokines are increased in children with cystic fibrosis. Eur. Respir. J. 2009, 34, 655–661.
  104. Bruscia, E.M.; Zhang, P.-X.; Ferreira, E.; Caputo, C.; Emerson, J.W.; Tuck, D.; Krause, D.S.; Egan, M.E. Macrophages directly contribute to the exaggerated inflammatory response in cystic fibrosis transmembrane conductance regulator−/− mice. Am. J. Respir. Cell Mol. Biol. 2009, 40, 295–304.
  105. Del Porto, P.; Cifani, N.; Guarnieri, S.; Di Domenico, E.G.; Mariggiò, M.A.; Spadaro, F.; Guglietta, S.; Anile, M.; Venuta, F.; Quattrucci, S.; et al. Dysfunctional CFTR alters the bactericidal activity of human macrophages against Pseudomonas Aeruginosa. PLoS ONE 2011, 6, e19970.
  106. Painter, R.G.; Valentine, V.G.; Lanson, N.A.; Leidal, K.; Zhang, Q.; Lombard, G.; Thompson, C.; Viswanathan, A.; Nauseef, W.M.; Wang, G.; et al. CFTR expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis. Biochemistry 2006, 45, 10260–10269.
  107. Moss, R.B.; Bocian, R.C.; Hsu, Y.P.; Dong, Y.J.; Kemna, M.; Wei, T.; Gardner, P. Reduced IL-10 secretion by CD4+ T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR). Clin. Exp. Immunol. 1996, 106, 374–388.
  108. Gao, Z.; Su, X. CFTR regulates acute inflammatory responses in macrophages. QJM Mon. J. Assoc. Phys. 2015, 108, 951–958.
  109. Wang, H.; Cebotaru, L.; Lee, H.W.; Yang, Q.; Pollard, B.S.; Pollard, H.B.; Guggino, W.B. CFTR controls the activity of NF-ΚB by enhancing the degradation of TRADD. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2016, 40, 1063–1078.
  110. Nakajima, S.; Hiramatsu, N.; Hayakawa, K.; Saito, Y.; Kato, H.; Huang, T.; Yao, J.; Paton, A.W.; Paton, J.C.; Kitamura, M. Selective abrogation of BiP/GRP78 blunts activation of NF-ΚB through the ATF6 branch of the UPR: Involvement of C/EBPβ and MTOR-dependent dephosphorylation of Akt. Mol. Cell. Biol. 2011, 31, 1710–1718.
  111. Yu, Y.; Zhang, L.; Liu, Q.; Tang, L.; Sun, H.; Guo, H. Endoplasmic reticulum stress preconditioning antagonizes low-density lipoprotein-induced inflammation in human mesangial cells through upregulation of XBP1 and suppression of the IRE1α/IKK/NF-ΚB pathway. Mol. Med. Rep. 2015, 11, 2048–2054.
  112. Chiang, S.-H.; Bazuine, M.; Lumeng, C.N.; Geletka, L.M.; Mowers, J.; White, N.M.; Ma, J.-T.; Zhou, J.; Qi, N.; Westcott, D.; et al. The protein kinase IKKepsilon regulates energy balance in obese mice. Cell 2009, 138, 961–975.
  113. Hu, P.; Han, Z.; Couvillon, A.D.; Kaufman, R.J.; Exton, J.H. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-KappaB activation and down-regulation of TRAF2 expression. Mol. Cell. Biol. 2006, 26, 3071–3084.
  114. Tufanli, O.; Telkoparan Akillilar, P.; Acosta-Alvear, D.; Kocaturk, B.; Onat, U.I.; Hamid, S.M.; Çimen, I.; Walter, P.; Weber, C.; Erbay, E. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc. Natl. Acad. Sci. USA 2017, 114, E1395–E1404.
  115. Jiang, H.-Y.; Wek, S.A.; McGrath, B.C.; Scheuner, D.; Kaufman, R.J.; Cavener, D.R.; Wek, R.C. Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-KappaB in response to diverse cellular stresses. Mol. Cell. Biol. 2003, 23, 5651–5663.
  116. Keestra-Gounder, A.M.; Byndloss, M.X.; Seyffert, N.; Young, B.M.; Chávez-Arroyo, A.; Tsai, A.Y.; Cevallos, S.A.; Winter, M.G.; Pham, O.H.; Tiffany, C.R.; et al. NOD1 and NOD2 signalling links ER stress with inflammation. Nature 2016, 532, 394–397.
  117. Janssens, S.; Pulendran, B.; Lambrecht, B.N. Emerging functions of the unfolded protein response in immunity. Nat. Immunol. 2014, 15, 910–919.
  118. Gardner, B.M.; Pincus, D.; Gotthardt, K.; Gallagher, C.M.; Walter, P. Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response. Available online: https://pubmed.ncbi.nlm.nih.gov/23388626/ (accessed on 24 August 2020).
  119. Cui, W.; Li, J.; Ron, D.; Sha, B. The structure of the PERK kinase domain suggests the mechanism for its activation. Acta Crystallogr. D Biol. Crystallogr. 2011, 67 Pt 5, 423–428.
  120. Carrara, M.; Prischi, F.; Nowak, P.R.; Ali, M.M. Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling. EMBO J. 2015, 34, 1589–1600.
  121. Holcik, M.; Sonenberg, N. Translational control in stress and apoptosis. Nat. Rev. Mol. Cell Biol. 2005, 6, 318–327.
  122. Proud, C.G. EIF2 and the control of cell physiology. Semin. Cell Dev. Biol. 2005, 16, 3–12.
  123. Tang, A.C.; Saferali, A.; He, G.; Sandford, A.J.; Strug, L.J.; Turvey, S.E. Endoplasmic reticulum stress and chemokine production in cystic fibrosis airway cells: Regulation by STAT3 modulation. J. Infect. Dis. 2017, 215, 293–302.
  124. Tam, A.B.; Mercado, E.L.; Hoffmann, A.; Niwa, M. ER stress activates NF-ΚB by integrating functions of basal IKK activity, IRE1 and PERK. PLoS ONE 2012, 7, e45078.
  125. Paramasivan, S.; Bassiouni, A.; Shiffer, A.; Dillon, M.R.; Cope, E.K.; Cooksley, C.; Ramezanpour, M.; Moraitis, S.; Ali, M.J.; Bleier, B.; et al. The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology. Allergy 2020, 75, 2037–2049.
  126. Coburn, B.; Wang, P.W.; Diaz Caballero, J.; Clark, S.T.; Brahma, V.; Donaldson, S.; Zhang, Y.; Surendra, A.; Gong, Y.; Elizabeth Tullis, D.; et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci. Rep. 2015, 5, 10241.
  127. Vongthilath, R.; Richaud Thiriez, B.; Dehillotte, C.; Lemonnier, L.; Guillien, A.; Degano, B.; Dalphin, M.-L.; Dalphin, J.-C.; Plésiat, P. Clinical and microbiological characteristics of cystic fibrosis adults never colonized by Pseudomonas Aeruginosa: Analysis of the French CF registry. PLoS ONE 2019, 14, e0210201.
  128. Lipuma, J.J. The changing microbial epidemiology in cystic fibrosis. Clin. Microbiol. Rev. 2010, 23, 299–323.
  129. Stecenko, A.A.; King, G.; Torii, K.; Breyer, R.M.; Dworski, R.; Blackwell, T.S.; Christman, J.W.; Brigham, K.L. Dysregulated cytokine production in human cystic fibrosis bronchial epithelial cells. Inflammation 2001, 25, 145–155.
  130. Medzhitov, R. Recognition of microorganisms and activation of the immune response. Nature 2007, 449, 819–826.
  131. Moreira, L.O.; Zamboni, D.S. NOD1 and NOD2 signaling in infection and inflammation. Front. Immunol. 2012, 3, 328.
  132. Chmiel, J.F.; Berger, M.; Konstan, M.W. The role of inflammation in the pathophysiology of CF lung disease. Clin. Rev. Allergy Immunol. 2002, 23, 5–27.
  133. Bedi, B.; Maurice, N.M.; Ciavatta, V.T.; Lynn, K.S.; Yuan, Z.; Molina, S.A.; Joo, M.; Tyor, W.R.; Goldberg, J.B.; Koval, M.; et al. Peroxisome proliferator-activated receptor-γ agonists attenuate biofilm formation by Pseudomonas Aeruginosa. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2017, 31, 3608–3621.
  134. Ahmadian, M.; Myoung Suh, J.; Hah, N.; Liddle, C.; Atkins, A.R.; Downes, M.; Evans, R.M. PPARγ Signaling and Metabolism: The Good, the Bad and the Future. Available online: https://pubmed.ncbi.nlm.nih.gov/23652116/ (accessed on 24 August 2020).
  135. Smith, J.A. Regulation of cytokine production by the unfolded protein response; implications for infection and autoimmunity. Front. Immunol. 2018, 9, 422.
  136. Bedi, B.; Lin, K.-C.; Maurice, N.M.; Yuan, Z.; Bijli, K.; Koval, M.; Hart, C.M.; Goldberg, J.B.; Stecenko, A.; Sadikot, R.T. UPR modulation of host immunity by Pseudomonas Aeruginosa in cystic fibrosis. Clin. Sci. Lond. Engl. 2020, 134, 1911–1934.
  137. Grootjans, J.; Kaser, A.; Kaufman, R.J.; Blumberg, R.S. The unfolded protein response in immunity and inflammation. Nat. Rev. Immunol. 2016, 16, 469–484.
  138. Paton, A.W.; Srimanote, P.; Talbot, U.M.; Wang, H.; Paton, J.C. A new family of potent AB(5) cytotoxins produced by shiga toxigenic Escherichia Coli. J. Exp. Med. 2004, 200, 35–46.
  139. Shenderov, K.; Riteau, N.; Yip, R.; Mayer-Barber, K.D.; Oland, S.; Hieny, S.; Fitzgerald, P.; Oberst, A.; Dillon, C.P.; Green, D.R.; et al. Cutting edge: Endoplasmic reticulum stress licenses macrophages to produce mature IL-1β in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway. J. Immunol. 2014, 192, 2029–2033.
  140. Duvigneau, J.C.; Luís, A.; Gorman, A.M.; Samali, A.; Kaltenecker, D.; Moriggl, R.; Kozlov, A.V. Crosstalk between inflammatory mediators and endoplasmic reticulum stress in liver diseases. Cytokine 2019, 124, 154577.
  141. Dalet, A.; Argüello, R.J.; Combes, A.; Spinelli, L.; Jaeger, S.; Fallet, M.; Vu Manh, T.-P.; Mendes, A.; Perego, J.; Reverendo, M.; et al. Protein synthesis inhibition and GADD34 control IFN-β heterogeneous expression in response to DsRNA. EMBO J. 2017, 36, 761–782.
  142. Cláudio, N.; Dalet, A.; Gatti, E.; Pierre, P. Mapping the crossroads of immune activation and cellular stress response pathways. EMBO J. 2013, 32, 1214–1224.
  143. Tilney, L.G.; Harb, O.S.; Connelly, P.S.; Robinson, C.G.; Roy, C.R. How the parasitic bacterium Legionella Pneumophila modifies its phagosome and transforms it into rough ER: Implications for conversion of plasma membrane to the ER membrane. J. Cell Sci. 2001, 114 Pt 24, 4637–4650.
  144. Hempstead, A.D.; Isberg, R.R. Inhibition of host cell translation elongation by Legionella Pneumophila blocks the host cell unfolded protein response. Proc. Natl. Acad. Sci. USA 2015, 112, E6790–E6797.
  145. Radhakrishnan, G.K.; Harms, J.S.; Splitter, G.A. Modulation of microtubule dynamics by a TIR domain protein from the intracellular pathogen Brucella Melitensis. Biochem. J. 2011, 439, 79–83.
  146. Shima, K.; Klinger, M.; Schütze, S.; Kaufhold, I.; Solbach, W.; Reiling, N.; Rupp, J. The role of endoplasmic reticulum-related BiP/GRP78 in interferon gamma-induced persistent Chlamydia Pneumoniae infection. Cell. Microbiol. 2015, 17, 923–934.
  147. Webster, S.J.; Ellis, L.; O’Brien, L.M.; Tyrrell, B.; Fitzmaurice, T.J.; Elder, M.J.; Clare, S.; Chee, R.; Gaston, J.S.H.; Goodall, J.C. IRE1α mediates PKR activation in response to Chlamydia Trachomatis infection. Microbes Infect. 2016, 18, 472–483.
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