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Cited by 42Respiratory viral infections researchOcular Infections and TreatmentsNF-κB Signaling Pathways

Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection

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Bitko, Vira, Garmon, Nicolle E, Cao, Tin, Estrada, Benjamin, Oakes, John E, Lausch, Robert N, Barik, Sailen·2004·BMC Microbiology
DOI 10.1186/1471-2180-4-28PMC PMC481065
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Abstract

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease. However, the exact natural route of RSV infection and its etiology remain relatively unknown. In this paper, we test the hypothesis that human corneal epithelial cells, which constitute the outermost layer of the cornea, can be infected with RSV, and that the infection leads to the activation of proinflammatory macromolecules. RESULTS: Corneal swabs obtained from pediatric patients with acute respiratory disease were found to contain RSV at a high frequency (43 positive out of 72 samples, i.e., 60%). Primary corneal epithelial cells in tissue culture supported robust infection and productive growth of RSV. Infection resulted in the activation of TNF-alpha, IL-6 and sixteen chemokines as well as NF-kappa B. Three proinflammatory CXC chemokines (MIG, I-TAC, IP-10) underwent the greatest activation. CONCLUSIONS: The ocular epithelium is readily infected by RSV. The pro-inflammatory cytokines are likely to play critical roles in the etiology of inflammation and conjunctivitis commonly seen in pediatric patients with respiratory infections. RSV-eye interactions have important implications in RSV transmission, immunopathology of RSV disease, and in the management of conjunctivitis.

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  • TNF-α is increased in tears during infections and inflammations of the cornea.

    “This is because TNF-α is increased in tears during infections and inflammations of the cornea, suggesting its importance as a mediator of inflammation in vitro as well as in vivo (Bitko et al., 2004; Kumar et al., 2004; Saika et al., 2005).”

    From Thymosin beta 4 suppression of corneal NFκB: A potential anti-inflammatory pathway (2007) · cites this paper as Bitko et al., 2004

    The Results section (‘Elaboration of interleukins by RSV-infected corneal epithelial cells’; page unavailable) reports increased TNF-α protein in the culture medium after RSV infection. That supports TNF-α production by infected corneal cells in vitro, but the paper does not report increased TNF-α in tears during corneal infection or inflammation in vivo. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The use of TNF-α as a pro-inflammatory stimulus in the cell culture model has important physiological relevance to corneal inflammation and epithelial wound healing.

    “The use of TNF-α as a pro-inflammatory stimulus in our cell culture model has important physiological relevance to corneal inflammation and epithelial wound healing.”

    From Thymosin beta 4 suppression of corneal NFκB: A potential anti-inflammatory pathway (2007) · cites this paper as Bitko et al., 2004

    The Abstract’s Results report that RSV infection activates TNF-α in cultured corneal epithelial cells, supporting a connection between TNF-α and corneal inflammatory responses. The paper studies RSV infection, not TNF-α used as a stimulus, and the passages do not address epithelial wound healing (searched: “wound healing” and “TNF-α pro-inflammatory stimulus”). (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 48

  1. Thompson WW Shay DK Weintraub E Brammer L Cox N Anderson LJ Fukuda K Mortality associated with influenza and respiratory syncytial virus in the United States JAMA 2003 289 179 186 12517228 10.1001/jama.289.2.179 · DOI · Paper page
  2. Maggon K Barik S New drugs and treatment for respiratory syncytial virus Rev Med Virol 2004 14 149 168 15124232 10.1002/rmv.423 · DOI
  3. Marriott AC Easton AJ Reverse genetics of the Paramyxoviridae Adv Virus Res 1999 53 321 340 10582105
  4. Welliver RC Respiratory syncytial virus and other respiratory viruses Pediatr Infect Dis J 2003 22 S6 S12 12671447 10.1097/00006454-200302001-00002 · DOI
  5. Greenough A Respiratory syncytial virus infection: clinical features, management, and prophylaxis Curr Opin Pulm Med 2002 8 214 217 11981311 10.1097/00063198-200205000-00011 · DOI
  6. Bitko V Velazquez A Yang L Yang YC Barik S Transcriptional activation of multiple cytokines by respiratory syncytial virus requires activation of NF-κB and is inhibited by sodium salicylate and aspirin Virology 1997 232 369 378 9191851 10.1006/viro.1997.8582 · DOI
  7. Bitko V Oldenburg A Garmon NE Barik S Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus BMC Microbiol 2003 3 9 12740026 10.1186/1471-2180-3-9 PMC156654 · DOI
  8. Tumpey TM Cheng H Cook DN Smithies O Oakes JE Lausch RN Absence of macrophage inflammatory protein-1 alpha prevents the development of blinding herpes stromal keratitis J Virol 1998 72 3705 3710 9557652 PMC109592
  9. Kumaraguru U Davis I Rouse BT Chemokines and ocular pathology caused by corneal infection with herpes simplex virus J Neurovirol 1999 5 42 47 10190689
  10. Gala CL Hall CB Schnabel KC Pincus PH Blossom P Hildreth SW Betts RF Douglas RG Jr The use of eye-nose goggles to control nosocomial respiratory syncytial virus infection JAMA 1986 256 2706 2708 3773177 10.1001/jama.256.19.2706 · DOI
  11. Hall CB Douglas RG Jr Schnabel KC Geiman JM Infectivity of respiratory syncytial virus by various routes of inoculation Infect Immun 1981 33 779 783 7287181 PMC350778
  12. Fujishima H Okamoto Y Saito I Tsubota K Respiratory syncytial virus and allergic conjunctivitis J Allergy Clin Immunol 1995 95 663 667 7897147
  13. Fujishima H Saito I Okamoto Y Takeuchi T Tsubota K Respiratory syncytial virus- induced interleukin-4 production by human conjunctival epithelial cells contributes to allergy: preliminary study Curr Eye Res 1998 17 656 662 9663856 10.1076/ceyr.17.6.656.5181 · DOI
  14. Fujishima H Respiratory syncytial virus may be a pathogen in allergic conjunctivitis Cornea 2002 21 S39 45 11995809 10.1097/00003226-200203001-00009 · DOI
  15. Tian B Zhang Y Luxon BA Garofalo RP Casola A Sinha M Brasier AR Identification of NF-kappaB-dependent gene networks in respiratory syncytial virus-infected cells J Virol 2002 76 6800 6814 12050393 10.1128/JVI.76.13.6800-6814.2002 PMC136270 · DOI
  16. Zhang Y Luxon BA Casola A Garofalo RP Jamaluddin M Brasier AR Expression of respiratory syncytial virus-induced chemokine gene networks in lower airway epithelial cells revealed by cDNA microarrays J Virol 2001 75 9044 9058 11533168 10.1128/JVI.75.19.9044-9058.2001 PMC114473 · DOI
  17. Haeberle HA Kuziel WA Dieterich HJ Casola A Gatalica Z Garofalo RP Inducible expression of inflammatory chemokines in respiratory syncytial virus-infected mice: role of MIP-1alpha in lung pathology J Virol 2001 75 878 890 11134301 10.1128/JVI.75.2.878-890.2001 PMC113984 · DOI
  18. Baggiolini M Chemokines in pathology and medicine J Intern Med 2001 250 91 104 11489059 10.1046/j.1365-2796.2001.00867.x · DOI
  19. Bacon K Baggiolini M Broxmeyer H Horuk R Lindley I Mantovani A Maysushima K Murphy P Nomiyama H Oppenheim J Rot A Schall T Tsang M Thorpe R Van Damme J Wadhwa M Yoshie O Zlotnik A Zoon K IUIS/WHO Subcommittee on Chemokine Nomenclature. Chemokine/chemokine receptor nomenclature J Interferon Cytokine Res 2002 22 1067 1068 12433287 10.1089/107999002760624305 · DOI
  20. Perkins ND The Rel/NF-kappa B family: friend and foe Trends Biochem Sci 2000 25 434 440 10973057 10.1016/S0968-0004(00)01617-0 · DOI
  21. Garofalo R Sabry M Jamaluddin M Yu RK Casola A Ogra PL Brasier AR Transcriptional activation of the interleukin-8 gene by respiratory syncytial virus infection in alveolar epithelial cells: nuclear translocation of the RelA transcription factor as a mechanism producing airway mucosal inflammation J Virol 1996 70 8773 8781 8971006 PMC190974
  22. Bitko V Barik S Persistent activation of RelA by respiratory syncytial virus involves protein kinase C, underphosphorylated IκBβ, and sequestration of protein phosphatase 2A by the viral phosphoprotein J Virol 1998 72 5610 5618 9621019 PMC110221
  23. Mastronarde JG He B Monick MM Mukaida N Matsushima K Hunninghake G Induction of IL-8 gene expression by respiratory syncytial virus involves activation of NF-κB and NF-IL-6 J Infect Dis 1996 174 262 267 8699053
  24. Fiedler MA Wernke-Dollries K Stark JM Inhibition of viral replication reverses respiratory syncytial virus-induced NF-kappa B activation and interleukin-8 gene expression in A549 cells J Virol 1996 70 9079 9082 8971048 PMC191016
  25. Bitko V Barik S Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses BMC Microbiol 2001 1 34 11801185 10.1186/1471-2180-1-34 PMC64570 · DOI
  26. Bitko V Barik S An endoplasmic reticulum-specific stress-activated caspase (caspase-12) is implicated in the apoptosis of A549 epithelial cells by respiratory syncytial virus J Cell Biochem 2001 80 441 454 11135374 10.1002/1097-4644(20010301)80:3<441::AID-JCB170>3.0.CO;2-C · DOI
  27. Dinarello CA Anti-cytokine therapeutics and infections Vaccine 2003 21 S24 34 12763679
  28. O'Neill LA Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily Curr Top Microbiol Immunol 2002 270 47 61 12467243
  29. Burns K Martinon F Tschopp J New insights into the mechanism of IL-1beta maturation Curr Opin Immunol 2003 15 26 30 12495729 10.1016/S0952-7915(02)00017-1 · DOI
  30. Thornberry NA Bull HG Calaycay JR Chapman KT Howard AD Kostura MJ Miller DK Molineaux SM Weidner JR Aunins J Elliston KO Ayala JM Casano FJ Chin J Ding GJF Egger LA Gaffney EP Limjuco G Palyha OC Raju SM Rolando AM Salley JP Yamin TT Lee TD Shively JE MacCross M Mumford RA Schmidt JA Tocci MJ A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes Nature 1992 356 768 774 1574116 10.1038/356768a0 · DOI
  31. Kopp E Ghosh S Inhibition of NF-κB by sodium salicylate and aspirin Science 1994 265 956 959 8052854
  32. Ishiguro N Takada A Yoshioka M Ma X Kikuta H Kida H Kobayashi K Induction of interferon-inducible protein-10 and monokine induced by interferon-gamma from human endothelial cells infected with influenza A virus Arch Virol 2004 149 17 34 14689273 10.1007/s00705-003-0208-4 · DOI
  33. Mahalingam S Chaudhri G Tan CL John A Foster PS Karupiah G Transcription of the interferon gamma (IFN-gamma)-inducible chemokine Mig in IFN-gamma-deficient mice J Biol Chem 2001 276 7568 7574 11024052 10.1074/jbc.M005773200 · DOI
  34. Staats HF Lausch RN Cytokine expression in vivo during murine herpetic stromal keratitis. Effect of protective antibody therapy J Immunol 1993 151 277 283 8392096
  35. Cubitt CL Lausch RN Oakes JE Differential induction of GROα gene expression in human corneal epithelial cells and keratinocytes exposed to proinflammatory cytokines Invest Opthalmol Vis Sci 1997 38 1149 1158 9152234
  36. Cubitt CL Tang Q Monterio CA Lausch RN Oakes JE IL-8 gene expression in cultures of human corneal epithelial cells and keratocytes Invest Opthalmol Vis Sci 1993 34 3199 3206 7691777
  37. Arrunategui-Correa V Baltatzis S Foster CS The role of cytokines in experimental herpes simplex keratitis Acta Virol 1999 43 325 329 10757234
  38. Yan XT Tumpey TM Kunkel SL Oakes JE Lausch RN Role of MIP-2 in neutrophil migration and tissue injury in the herpes simplex virus-1-infected cornea Invest Ophthalmol Vis Sci 1998 39 1854 1862 9727408
  39. Hendricks RL Immunopathogenesis of viral ocular infections Chem Immunol 1999 73 120 136 10590577
  40. Koulikovska M van der Ploeg I Herrmann B Montan PG Respiratory syncytial virus and chlamydia are not detectable by PCR in ongoing vernal keratoconjunctivitis Ocul Immunol Inflamm 2001 9 253 257 11935435 10.1076/ocii.9.4.253.3955 · DOI
  41. Yoshida K Hu Y Karin M IkappaB kinase alpha is essential for development of the mammalian cornea and conjunctiva Invest Ophthalmol Vis Sci 2000 41 3665 3669 11053261
  42. Glass WG Rosenberg HF Murphy PM Chemokine regulation of inflammation during acute viral infection Curr Opin Allergy Clin Immunol 2003 3 467 473 14612671 10.1097/00130832-200312000-00008 · DOI
  43. Bonville CA Easton AJ Rosenberg HF Domachowske JB Altered pathogenesis of severe pneumovirus infection in response to combined antiviral and specific immunomodulatory agents J Virol 2003 77 1237 1244 12502841 10.1128/JVI.77.2.1237-1244.2003 PMC140832 · DOI
  44. Grondahl B Puppe W Hoppe A Kuhne I Weigl JA Schmitt HJ Rapid identification of nine microorganisms causing acute respiratory tract infections by single-tube multiplex RT-PCR: feasibility study J Clin Microbiol 1999 37 1 7 9854054 PMC84151
  45. Laemmli UK Cleavage of structural proteins during the assembly of the head of bacteriophage T4 Nature 1970 227 680 685 5432063
  46. Barik S McLean T Dupuy L Phosphorylation of Ser232 directly regulates the transcriptional activity of the P protein of human respiratory syncytial virus: Phosphorylation of Ser237 may play an accessory role Virology 1995 213 405 412 7491765 10.1006/viro.1995.0013 · DOI
  47. Burke E Dupuy L Wall C Barik S Role of cellular actin in the gene expression and morphogenesis of human respiratory syncytial virus Virology 1998 252 137 148 9875324 10.1006/viro.1998.9471 · DOI
  48. Barik S Mutagenesis and gene fusion by megaprimer PCR Methods Mol Biol 1997 67 173 181 9031141

Cited by

Sorted by citations

Authors
Bitko, V., Garmon, N. E., Cao, T., Estrada, B., Oakes, J. E., Lausch, R. N., & Barik, S.
Affiliations
University of South Alabama (US)
Corresponding author
Barik, Sailen
ORCID
Barik, Sailen
Venue
BMC Microbiology
Publisher
Springer Science and Business Media LLC
Published
2004-07-15
Volume
4
Issue
1
Pages
28-28
ISSN
1471-2180 (ISSN-L)
DOI
10.1186/1471-2180-4-28
PMC
PMC481065
OpenAlex
W1614381545
Cited by
42
References
0
Citations by year
2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
FWCI
3.61
Type
journal article
Language
en
Open access
Locations
  • BMC Microbiology (publishedVersion)
  • PubMed Central (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Institutes of Health (R01‐grant)
  • National Eye Institute (R01EY013826)
  • National Institute of Allergy and Infectious Diseases (F32AI049682, R01 F32 AI049682)
Topics
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
respiratory syncytial virus, corneal epithelial cells, ocular infection, NF-κB activation, inflammatory cytokines, chemokines, TNF-α, interleukin-6, CXC chemokines, conjunctivitis, pediatric respiratory infection, ocular inflammation
MeSH terms
Child, Child, Preschool, Conjunctivitis, Viral, Humans, Respiratory Tract Infections, RNA, Messenger, Virus Replication, Giant Cells, Cytokines, NF-kappa B, Respiratory Syncytial Virus, Human, Respiratory Syncytial Virus Infections, Epithelium, Corneal, Reverse Transcriptase Polymerase Chain Reaction, In Vitro Techniques

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