Newborn cystic fibrosis pigs have a blunted early response to an inflammatory stimulus

American Journal of Respiratory and Critical Care Medicine

Volumn 194, Issue 7, 2016, Pages 845-854

  Bartlett, Jennifer A ^a   Ramachandran, Shyam ^a,b   Wohlford Lenane, Christine L ^a   Barker, Carrie K ^a   Pezzulo, Alejandro A ^a   Zabner, Joseph ^a   Welsh, Michael J ^a   Meyerholz, David K ^a   Stoltz, David A ^a   McCray, Paul B ^a  

^a UNIVERSITY OF IOWA   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

Airway epithelia; Inflammation; Staphylococcus aureus; Transcriptional profiling

Indexed keywords

BCLAF1 PROTEIN; CASP3 PROTEIN; CASP6 PROTEIN; CASP7 PROTEIN; CYCLOOXYGENASE 2; FASLG PROTEIN; FASR PROTEIN; HIF1A PROTEIN; ICAM1 PROTEIN; IL1A PROTEIN; IL1B PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; INTERLEUKIN 8; MESSENGER RNA; NFKBIA PROTEIN; PROTEIN; PROTEIN BCL 10; RNA; ROCK1 PROTEIN; TGFB1 PROTEIN; TRANSCRIPTION FACTOR MSX1; TRANSCRIPTOME; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COLONY FORMING UNIT; CONTROLLED STUDY; CYSTIC FIBROSIS; CYTOKINE PRODUCTION; CYTOKINE RESPONSE; DOWN REGULATION; GENE EXPRESSION PROFILING; GENETIC TRANSCRIPTION; GENOTYPE; HOST RESISTANCE; IN VITRO STUDY; IN VIVO STUDY; INFECTION; INFLAMMATION; LUNG LAVAGE; NEUTROPHIL; NEWBORN; NONHUMAN; PORCINE MODEL; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA ISOLATION; RNA SEQUENCE; STIMULUS RESPONSE; TRANSCRIPTOMICS; ANIMAL; APOPTOSIS; CELL PROLIFERATION; COMPARATIVE STUDY; DISEASE EXACERBATION; EPITHELIUM; GENETICS; IMMUNOLOGY; LUNG; MICROBIOLOGY; PIG; RESPIRATORY MUCOSA; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS;

ANIMALS; ANIMALS, NEWBORN; APOPTOSIS; CELL PROLIFERATION; CYSTIC FIBROSIS; DISEASE PROGRESSION; EPITHELIUM; GENOTYPE; IN VITRO TECHNIQUES; INFLAMMATION; LUNG; MODELS, ANIMAL; RESPIRATORY MUCOSA; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; SWINE; TRANSCRIPTOME;

EID: 84992436652     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201510-2112OC     Document Type: Article

References (63)

1. Cohen-Cymberknoh M, Kerem E, Ferkol T, Elizur A. Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications. Thorax 2013;68:1157-1162.
2. Stoltz DA, Meyerholz DK, Welsh MJ. Origins of cystic fibrosis lung disease. N Engl J Med 2015;372:351-362.
3. Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, et al. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 2008;321:1837-1841.
4. Stoltz DA, Meyerholz DK, Pezzulo AA, Ramachandran S, Rogan MP, Davis GJ, Hanfland RA, Wohlford-Lenane C, Dohrn CL, Bartlett JA, et al. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth. Sci Transl Med 2010;2:29ra31.
5. Bartlett JA, Ramachandran S, Wohlford-Lenane C, Barker CK, Manzel L, Pezzulo AA, Zabner J, Welsh MJ, Colby J, Levy BD, et al. Acute inflammatory responses to bacterial challenge in newborn CF and non-CF pigs [abstract]. Pediatr Pulmonol Suppl 2013;36:235.
6. Bartlett JA, Wohlford-Lenane C, Barker C, Ramachandran S, Manzel L, Pezzulo A, Zabner J, Welsh MJ, Colby J, Levy BD, et al. Pulmonary inflammatory responses to bacterial challenge in newborn CF and non-CF pigs [abstract]. Pediatr Pulmonol Suppl 2012;35:255-256.
7. Karp PH, Moninger TO, Weber SP, Nesselhauf TS, Launspach JL, Zabner J, Welsh MJ. An in vitro model of differentiated human airway epithelia. Methods for establishing primary cultures. Methods Mol Biol 2002;188:115-137.
8. Ramachandran S, Clarke LA, Scheetz TE, Amaral MD, McCray PB Jr. Microarray mRNA expression profiling to study cystic fibrosis. Methods Mol Biol 2011;742:193-212.
9. Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP. GenePattern 2.0. Nat Genet 2006;38:500-501.
10. Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009;37:1-13.
11. Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009;4:44-57.
12. Eden E, Lipson D, Yogev S, Yakhini Z. Discovering motifs in ranked lists of DNA sequences. PLOS Comput Biol 2007;3:e39.
13. Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z. GOrilla: A tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics 2009;10:48.
14. Szaff M, Høiby N. Antibiotic treatment of Staphylococcus aureus infection in cystic fibrosis. Acta Paediatr Scand 1982;71:821-826.
15. Pezzulo AA, Tang XX, Hoegger MJ, Alaiwa MH, Ramachandran S, Moninger TO, Karp PH, Wohlford-Lenane CL, Haagsman HP, van Eijk M, et al. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature 2012;487:109-113.
16. Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL,Wold BJ, Pachter L. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 2010;28:511-515.
17. Carrabino S, Carpani D, Livraghi A, Di Cicco M, Costantini D, Copreni E, Colombo C, Conese M. Dysregulated interleukin-8 secretion and NF-kappaB activity in human cystic fibrosis nasal epithelial cells. J Cyst Fibros 2006;5:113-119.
18. DiMango E, Zar HJ, Bryan R, Prince A. Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J Clin Invest 1995;96:2204-2210.
19. Eidelman O, Srivastava M, Zhang J, Leighton X, Murtie J, Jozwik C, Jacobson K, Weinstein DL, Metcalf EL, Pollard HB. Control of the proinflammatory state in cystic fibrosis lung epithelial cells by genes from the TNF-alphaR/NFkappaB pathway. Mol Med 2001;7: 523-534.
20. Joseph T, Look D, Ferkol T. NF-kB activation and sustained IL-8 gene expression in primary cultures of cystic fibrosis airway epithelial cells stimulated with Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol Physiol 2005;288:L471-L479.
21. Kammouni W, Figarella C, Baeza N, Marchand S, Merten MD. Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells. Biochem Biophys Res Commun 1997;241:305-311.
22. Kammouni W, Figarella C, Marchand S, Merten M. Altered cytokine production by cystic fibrosis tracheal gland serous cells. Infect Immun 1997;65:5176-5183.
23. Kelley TJ, Drumm ML. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest 1998;102:1200-1207.
24. Kube D, Sontich U, Fletcher D, Davis PB. Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines. Am J Physiol Lung Cell Mol Physiol 2001;280:L493-L502.
25. Massengale AR, Quinn F Jr, Yankaskas J, Weissman D, McClellan WT, Cuff C, Aronoff SC. Reduced interleukin-8 production by cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol 1999;20: 1073-1080.
26. Reiniger N, Ichikawa JK, Pier GB. Influence of cystic fibrosis transmembrane conductance regulator on gene expression in response to Pseudomonas aeruginosa infection of human bronchial epithelial cells. Infect Immun 2005;73:6822-6830.
27. Stecenko AA, King G, Torii K, Breyer RM, Dworski R, Blackwell TS, Christman JW, Brigham KL. Dysregulated cytokine production in human cystic fibrosis bronchial epithelial cells. Inflammation 2001; 25:145-155.
28. Tabary O, Escotte S, Couetil JP, Hubert D, Dusser D, Puchelle E, Jacquot J. High susceptibility for cystic fibrosis human airway gland cells to produce IL-8 through the IkB kinase alpha pathway in response to extracellular NaCl content. J Immunol 2000;164: 3377-3384.
29. Venkatakrishnan A, Stecenko AA, King G, Blackwell TR, Brigham KL, Christman JW, Blackwell TS. Exaggerated activation of nuclear factor-kB and altered IkB-b processing in cystic fibrosis bronchial epithelial cells. Am J Respir Cell Mol Biol 2000;23:396-403.
30. Tirouvanziam R, de Bentzmann S, Hubeau C, Hinnrasky J, Jacquot J, Péault B, Puchelle E. Inflammation and infection in naive human cystic fibrosis airway grafts. Am J Respir Cell Mol Biol 2000;23: 121-127.
31. Bensalem N, Ventura AP, Valleé B, Lipecka J, Tondelier D, Davezac N, Dos Santos A, Perretti M, Fajac A, Sermet-Gaudelus I, et al. Down-regulation of the anti-inflammatory protein annexin A1 in cystic fibrosis knock-out mice and patients. Mol Cell Proteomics 2005;4:1591-1601.
32. Kelley TJ, Elmer HL. In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic fibrosis epithelium. J Clin Invest 2000; 106:403-410.
33. Heeckeren A, Walenga R, Konstan MW, Bonfield T, Davis PB, Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J Clin Invest 1997;100:2810-2815.
34. Perez A, Issler AC, Cotton CU, Kelley TJ, Verkman AS, Davis PB. CFTR inhibition mimics the cystic fibrosis inflammatory profile. Am J Physiol Lung Cell Mol Physiol 2007;292:L383-L395.
35. Verhaeghe C, Delbecque K, de Leval L, Oury C, Bours V. Early inflammation in the airways of a cystic fibrosis foetus. J Cyst Fibros 2007;6:304-308.
36. Verhaeghe C, Remouchamps C, Hennuy B, Vanderplasschen A, Chariot A, Tabruyn SP, Oury C, Bours V. Role of IKK and ERK pathways in intrinsic inflammation of cystic fibrosis airways. Biochem Pharmacol 2007;73:1982-1994.
37. Weber AJ, Soong G, Bryan R, Saba S, Prince A. Activation of NF-kB in airway epithelial cells is dependent on CFTR trafficking and Cl-channel function. Am J Physiol Lung Cell Mol Physiol 2001;281:L71-L78.
38. Vij N, Mazur S, Zeitlin PL. CFTR is a negative regulator of NFkB mediated innate immune response. PLoS One 2009;4:e4664.
39. Becker MN, Sauer MS, Muhlebach MS, Hirsh AJ, Wu Q, Verghese MW, Randell SH. Cytokine secretion by cystic fibrosis airway epithelial cells. Am J Respir Crit Care Med 2004;169:645-653.
40. Black HR, Yankaskas JR, Johnson LG, Noah TL. Interleukin-8 production by cystic fibrosis nasal epithelial cells after tumor necrosis factor-alpha and respiratory syncytial virus stimulation. Am J Respir Cell Mol Biol 1998;19:210-215.
41. Hybiske K, Fu Z, Schwarzer C, Tseng J, Do J, Huang N, Machen TE. Effects of cystic fibrosis transmembrane conductance regulator and DeltaF508CFTR on inflammatory response, ER stress, and Ca21 of airway epithelia. Am J Physiol Lung Cell Mol Physiol 2007;293: L1250-L1260.
42. Aldallal N, McNaughton EE, Manzel LJ, Richards AM, Zabner J, Ferkol TW, Look DC. Inflammatory response in airway epithelial cells isolated from patients with cystic fibrosis. Am J Respir Crit Care Med 2002;166:1248-1256.
43. Fulcher ML, Gabriel S, Burns KA, Yankaskas JR, Randell SH. Welldifferentiated human airway epithelial cell cultures. Methods Mol Med 2005;107:183-206.
44. Keiser NW, Birket SE, Evans IA, Tyler SR, Crooke AK, Sun X, Zhou W, Nellis JR, Stroebele EK, Chu KK, et al. Defective innate immunity and hyper-inflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs. Am J Respir Cell Mol Biol 2015;52:683-693.
45. Leigh MW, Gambling TM, Carson JL, Collier AM, Wood RE, Boat TF. Postnatal development of tracheal surface epithelium and submucosal glands in the ferret. Exp Lung Res 1986;10:153-169.
46. Rottner M, Kunzelmann C, Mergey M, Freyssinet JM, Martínez MC. Exaggerated apoptosis and NF-kappaB activation in pancreatic and tracheal cystic fibrosis cells. FASEB J 2007;21:2939-2948.
47. Rottner M, Tual-Chalot S, Mostefai HA, Andriantsitohaina R, Freyssinet JM, Martínez MC. Increased oxidative stress induces apoptosis in human cystic fibrosis cells. PLoS One 2011;6:e24880.
48. Chaudhary N, Datta K, Askin FB, Staab JF, Marr KA. Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation. Am J Respir Crit Care Med 2012;185:301-310.
49. Bodas M, Min T, Vij N. Critical role of CFTR-dependent lipid rafts in cigarette smoke-induced lung epithelial injury. Am J Physiol Lung Cell Mol Physiol 2011;300:L811-L820.
50. Gottlieb E, Lindner S, Oren M. Relationship of sequence-specific transactivation and p53-regulated apoptosis in interleukin 3-dependent hematopoietic cells. Cell Growth Differ 1996;7:301-310.
51. Xu W, Zheng S, Goggans TM, Kiser P, Quinones-Mateu ME, Janocha AJ, Comhair SA, Slee R, Williams BR, Erzurum SC. Cystic fibrosis and normal human airway epithelial cell response to influenza a viral infection. J Interferon Cytokine Res 2006;26:609-627.
52. Rajan S, Cacalano G, Bryan R, Ratner AJ, Sontich CU, van Heerckeren A, Davis P, Prince A. Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells: analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors. Am J Respir Cell Mol Biol 2000;23:304-312.
53. Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peränen J, Merdes A, Slusarski DC, Scheller RH, Bazan JF, Sheffield VC, et al. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 2007;129:1201-1213.
54. Shah AS, Farmen SL, Moninger TO, Businga TR, Andrews MP, Bugge K, Searby CC, Nishimura D, Brogden KA, Kline JN, et al. Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia. Proc Natl Acad Sci USA 2008;105: 3380-3385.
55. Moore SJ, Green JS, Fan Y, Bhogal AK, Dicks E, Fernandez BA, Stefanelli M, Murphy C, Cramer BC, Dean JC, et al. Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: A 22-year prospective, population-based, cohort study. Am J Med Genet A 2005;132A:352-360.
56. Pazour GJ, Agrin N, Walker BL, Witman GB. Identification of predicted human outer dynein arm genes: candidates for primary ciliary dyskinesia genes. J Med Genet 2006;43:62-73.
57. Flight WG, Jones AM. Cystic fibrosis, primary ciliary dyskinesia and non-cystic fibrosis bronchiectasis: update 2008-11. Thorax 2012;67: 645-649.
58. Hui CC, Angers S. Gli proteins in development and disease. Annu Rev Cell Dev Biol 2011;27:513-537.
59. Bonfield TL, Hodges CA, Cotton CU, Drumm ML. Absence of the cystic fibrosis transmembrane regulator (CFTR) from myeloid-derived cells slows resolution of inflammation and infection. J Leukoc Biol 2012; 92:1111-1122.
60. Bruscia EM, Zhang PX, Ferreira E, Caputo C, Emerson JW, Tuck D, Krause DS, Egan ME. 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.
61. Di A, Brown ME, Deriy LV, Li C, Szeto FL, Chen Y, Huang P, Tong J, Naren AP, Bindokas V, et al. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat Cell Biol 2006;8:933-944.
62. Painter RG, Bonvillain RW, Valentine VG, Lombard GA, LaPlace SG, Nauseef WM, Wang G. The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophils. J Leukoc Biol 2008;83:1345-1353.
63. Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, et al. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science 2014;345:818-822.