Epithelial Cell Innate Responses to Rhinovirus Infection

  • Jean Kim
  • Robert Schleimer
Part of the Allergy Frontiers book series (ALLERGY, volume 2)

Rhinoviruses are a major cause of the common cold and play a significant role in the exacerbation of various diseases of the airways, including asthma, rhinosinusitis (CRS) and chronic obstructive pulmonary disease (COPD). In a normal person, they usually cause a self-limiting inflammatory response, mostly confined to the upper airways, and morbidity and mortality are minimal. In a patient with the above diseases, rhinovirus infection can cause a significant worsening of their preexisting disease and can cause life-threatening exacerbations. The purpose of this chapter is to briefly review the literature on the interaction of rhinoviruses with airway epithelium, the most important cellular target of rhinovirus infection, with the belief that improved knowledge of the molecular and cellular responses of the normal and diseased host with rhinovirus will lead to new opportunities to prevent exacerbations of airway diseases.


Chronic Obstructive Pulmonary Disease Bronchial Epithelial Cell Airway Epithelial Cell Internal Ribosomal Entry Site Human Bronchial Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gwaltney, J. M., Jr., J. O. Hendley, G. Simon, and W. S. Jordan, Jr. 1966. Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl J Med 275:1261.PubMedCrossRefGoogle Scholar
  2. 2.
    Nicholson, K. G., J. Kent, and D. C. Ireland. 1993. Respiratory viruses and exacerbations of asthma in adults. BMJ 307:982.PubMedCrossRefGoogle Scholar
  3. 3.
    Johnston, S. L., P. K. Pattemore, G. Sanderson, S. Smith, F. Lampe, L. Josephs, P. Symington, S. O'Toole, S. H. Myint, D. A. Tyrrell, and et al. 1995. Community study of role of viral infections in exacerbations of asthma in 9–11 year old children. BMJ 310:1225.Google Scholar
  4. 4.
    Rohde, G., A. Wiethege, I. Borg, M. Kauth, T. T. Bauer, A. Gillissen, A. Bufe, and G. Schultze-Werninghaus. 2003. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study. Thorax 58:37.PubMedCrossRefGoogle Scholar
  5. 5.
    Tan, W. C., X. Xiang, D. Qiu, T. P. Ng, S. F. Lam, and R. G. Hegele. 2003. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease. Am J Med 115:272.PubMedCrossRefGoogle Scholar
  6. 6.
    Green, R. M., A. Custovic, G. Sanderson, J. Hunter, S. L. Johnston, and A. Woodcock. 2002. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. BMJ 324:763.PubMedCrossRefGoogle Scholar
  7. 7.
    Murray, C. S., A. Simpson, and A. Custovic. 2004. Allergens, viruses, and asthma exacerbations. Proc Am Thorac Soc 1:99.PubMedCrossRefGoogle Scholar
  8. 8.
    Jones, J., C. Gable, M. Floor, J. Staffa, M. Rajan, M. Shaw, and C. Kennedy. 1993. Prior upper respiratory infection and allergic rhinitis: relationship to chronic sinusitis. Abstract from conference proceedings. In Int. Conf. on Sinus Disease.Google Scholar
  9. 9.
    Pitkaranta, A., E. Arruda, H. Malmberg, and F. G. Hayden. 1997. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J Clin Microbiol 35:1791.PubMedGoogle Scholar
  10. 10.
    Rueckert, R. 1996. Picornaviridae: The Viruses and Their Replication. In Fields Virology. B. Fields, D. Knipe, and P. Howley, eds. Lippincott-Raven, Philadelphia, p. 609.Google Scholar
  11. 11.
    McCray, J., and G. Werner. 1987. Different rhinovirus serotypes neutralized by antipeptide antibodies. Nature 329:736.PubMedCrossRefGoogle Scholar
  12. 12.
    Greve, J. M., C. P. Forte, C. W. Marlor, A. M. Meyer, H. Hoover-Litty, D. Wunderlich, and A. McClelland. 1991. Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1. J Virol 65:6015.PubMedGoogle Scholar
  13. 13.
    Staunton, D. E., V. J. Merluzzi, R. Rothlein, R. Barton, S. D. Marlin, and T. A. Springer. 1989. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell 56:849.PubMedCrossRefGoogle Scholar
  14. 14.
    Hofer, F., M. Gruenberger, H. Kowalski, H. Machat, M. Huettinger, E. Kuechler, and D. Blaas. 1994. Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci USA 91:1839.PubMedCrossRefGoogle Scholar
  15. 15.
    Uncapher, C. R., C. M. DeWitt, and R. J. Colonno. 1991. The major and minor group receptor families contain all but one human rhinovirus serotype. Virology 180:814.PubMedCrossRefGoogle Scholar
  16. 16.
    Snyers, L., H. Zwickl, and D. Blaas. 2003. Human rhinovirus type 2 is internalized by clathrin-mediated endocytosis. J Virol 77:5360.PubMedCrossRefGoogle Scholar
  17. 17.
    Wang, Q., G. R. Pfeiffer, 2nd, and W. A. Gaarde. 2003. Activation of SRC tyrosine kinases in response to ICAM-1 ligation in pulmonary microvascular endothelial cells. J Biol Chem 278:47731.PubMedCrossRefGoogle Scholar
  18. 18.
    Etienne, S., P. Adamson, J. Greenwood, A. D. Strosberg, S. Cazaubon, and P. O. Couraud. 1998. ICAM-1 signaling pathways associated with Rho activation in microvascular brain endothelial cells. J Immunol 161:5755.PubMedGoogle Scholar
  19. 19.
    Newcomb, D. C., U. Sajjan, S. Nanua, Y. Jia, A. M. Goldsmith, J. K. Bentley, and M. B. Hershenson. 2005. Phosphatidylinositol 3-kinase is required for rhinovirus-induced airway epithelial cell interleukin-8 expression. J Biol Chem 280:36952.PubMedCrossRefGoogle Scholar
  20. 20.
    Subauste, M. C., D. B. Jacoby, S. M. Richards, and D. Proud. 1995. Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. J Clin Invest 96:549.PubMedCrossRefGoogle Scholar
  21. 21.
    Bianco, A., S. K. Sethi, J. T. Allen, R. A. Knight, and M. A. Spiteri. 1998. Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1. Eur Respir J 12:619.PubMedCrossRefGoogle Scholar
  22. 22.
    Papi, A., and S. L. Johnston. 1999. Rhinovirus infection induces expression of its own receptor intercellular adhesion molecule 1 (ICAM-1) via increased NF-kappaB-mediated transcription. J Biol Chem 274:9707.PubMedCrossRefGoogle Scholar
  23. 23.
    Atsuta, J., S. A. Sterbinsky, J. Plitt, L. M. Schwiebert, B. S. Bochner, and R. P. Schleimer. 1997. Phenotyping and cytokine regulation of the BEAS-2B human bronchial epithelial cell: demonstration of inducible expression of the adhesion molecules VCAM-1 and ICAM-1. Am J Respir Cell Mol Biol 17:571.PubMedGoogle Scholar
  24. 24.
    Wang, X., C. Lau, S. Wiehler, A. Pow, T. Mazzulli, C. Gutierrez, D. Proud, and C. W. Chow. 2006. Syk is downstream of intercellular adhesion molecule-1 and mediates human rhinovirus activation of p38 MAPK in airway epithelial cells. J Immunol 177:6859.PubMedGoogle Scholar
  25. 25.
    Gern, J. E., and W. W. Busse. 2000. The role of viral infections in the natural history of asthma. J Allergy Clin Immunol 106:201.PubMedCrossRefGoogle Scholar
  26. 26.
    Seemungal, T. A., R. Harper-Owen, A. Bhowmik, D. J. Jeffries, and J. A. Wedzicha. 2000. Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease. Eur Respir J 16:677.PubMedCrossRefGoogle Scholar
  27. 27.
    Seemungal, T., R. Harper-Owen, A. Bhowmik, I. Moric, G. Sanderson, S. Message, P. Maccallum, T. W. Meade, D. J. Jeffries, S. L. Johnston, and J. A. Wedzicha. 2001. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164:1618.PubMedGoogle Scholar
  28. 28.
    Gern, J. E., E. C. Dick, W. M. Lee, S. Murray, K. Meyer, Z. T. Handzel, and W. W. Busse. 1996. Rhinovirus enters but does not replicate inside monocytes and airway macrophages. J Immunol 156:621.PubMedGoogle Scholar
  29. 29.
    Sanders, S. P., E. S. Siekierski, J. D. Porter, S. M. Richards, and D. Proud. 1998. Nitric oxide inhibits rhinovirus-induced cytokine production and viral replication in a human respiratory epithelial cell line. J Virol 72:934.PubMedGoogle Scholar
  30. 30.
    Stellato, C., L. A. Beck, G. A. Gorgone, D. Proud, T. J. Schall, S. J. Ono, L. M. Lichtenstein, and R. P. Schleimer. 1995. Expression of the chemokine RANTES by a human bronchial epithelial cell line. Modulation by cytokines and glucocorticoids. J Immunol 155:410.PubMedGoogle Scholar
  31. 31.
    Mosser, A. G., R. Vrtis, L. Burchell, W. M. Lee, C. R. Dick, E. Weisshaar, D. Bock, C. A. Swenson, R. D. Cornwell, K. C. Meyer, N. N. Jarjour, W. W. Busse, and J. E. Gern. 2005. Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues. Am J Respir Crit Care Med 171:645.PubMedCrossRefGoogle Scholar
  32. 32.
    Proud, D. 1993. Biology of Epithelial Cells. In Middleton's Allergy: Principles and Practice, Vol. 1. Middleton, ed. Elsevier, p. 373.Google Scholar
  33. 33.
    Korpi-Steiner, N. L., M. E. Bates, W. M. Lee, D. J. Hall, and P. J. Bertics. 2006. Human rhino-virus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation. J Leukoc Biol 80:1364.PubMedCrossRefGoogle Scholar
  34. 34.
    Hall, D. J., M. E. Bates, L. Guar, M. Cronan, N. Korpi, and P. J. Bertics. 2005. The role of p38 MAPK in rhinovirus-induced monocyte chemoattractant protein-1 production by monocytic-lineage cells. J Immunol 174:8056.PubMedGoogle Scholar
  35. 35.
    Gern, J. E., R. Vrtis, E. A. Kelly, E. C. Dick, and W. W. Busse. 1996. Rhinovirus produces nonspecific activation of lymphocytes through a monocyte-dependent mechanism. J Immunol 157:1605.PubMedGoogle Scholar
  36. 36.
    Proud, D., J. M. Gwaltney, Jr., J. O. Hendley, C. A. Dinarello, S. Gillis, and R. P. Schleimer. 1994. Increased levels of interleukin-1 are detected in nasal secretions of volunteers during experimental rhinovirus colds. J Infect Dis 169:1007.PubMedGoogle Scholar
  37. 37.
    Noah, T. L., F. W. Henderson, I. A. Wortman, R. B. Devlin, J. Handy, H. S. Koren, and S. Becker. 1995. Nasal cytokine production in viral acute upper respiratory infection of childhood. J Infect Dis 171:584.PubMedGoogle Scholar
  38. 38.
    Grunberg, K., M. C. Timmers, H. H. Smits, E. P. de Klerk, E. C. Dick, W. J. Spaan, P. S. Hiemstra, and P. J. Sterk. 1997. Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo. Clin Exp Allergy 27:36.PubMedCrossRefGoogle Scholar
  39. 39.
    Pizzichini, M. M., E. Pizzichini, A. Efthimiadis, A. J. Chauhan, S. L. Johnston, P. Hussack, J. Mahony, J. Dolovich, and F. E. Hargreave. 1998. Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study. Am J Respir Crit Care Med 158:1178.PubMedGoogle Scholar
  40. 40.
    van Benten, I. J., A. KleinJan, H. J. Neijens, A. D. Osterhaus, and W. J. Fokkens. 2001. Prolonged nasal eosinophilia in allergic patients after common cold. Allergy 56:949.PubMedCrossRefGoogle Scholar
  41. 41.
    Papadopoulos, N. G., A. Papi, J. Meyer, L. A. Stanciu, S. Salvi, S. T. Holgate, and S. L. Johnston. 2001. Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells. Clin Exp Allergy 31:1060.PubMedCrossRefGoogle Scholar
  42. 42.
    Greiff, L., M. Andersson, E. Andersson, M. Linden, S. Myint, C. Svensson, and C. G. Persson. 1999. Experimental common cold increases mucosal output of eotaxin in atopic individuals. Allergy 54:1204.PubMedCrossRefGoogle Scholar
  43. 43.
    Turner, R. B., K. W. Weingand, C. H. Yeh, and D. W. Leedy. 1998. Association between interleukin-8 concentration in nasal secretions and severity of symptoms of experimental rhinovirus colds. Clin Infect Dis 26:840.PubMedCrossRefGoogle Scholar
  44. 44.
    Johnston, S. L. 2003. Experimental models of rhinovirus-induced exacerbations of asthma: where to now? Am J Respir Crit Care Med 168:1145.PubMedCrossRefGoogle Scholar
  45. 45.
    Mosser, A. G., R. Brockman-Schneider, S. Amineva, L. Burchell, J. B. Sedgwick, W. W. Busse, and J. E. Gern. 2002. Similar frequency of rhinovirus-infectible cells in upper and lower airway epithelium. J Infect Dis 185:734.PubMedCrossRefGoogle Scholar
  46. 46.
    Papadopoulos, N. G., P. J. Bates, P. G. Bardin, A. Papi, S. H. Leir, D. J. Fraenkel, J. Meyer, P. M. Lackie, G. Sanderson, S. T. Holgate, and S. L. Johnston. 2000. Rhinoviruses infect the lower airways. J Infect Dis 181:1875.PubMedCrossRefGoogle Scholar
  47. 47.
    Winther, B., S. Brofeldt, H. Gronborg, and N. Mygind. 1983. Pathology of naturally occurring colds. Eur J Respir Dis Suppl 128 (Pt 1):345.PubMedGoogle Scholar
  48. 48.
    Winther, B., J. M. Gwaltney, Jr., N. Mygind, R. B. Turner, and J. O. Hendley. 1986. Sites of rhinovirus recovery after point inoculation of the upper airway. JAMA 256:1763.PubMedCrossRefGoogle Scholar
  49. 49.
    Yang, D., O. Chertov, S. N. Bykovskaia, Q. Chen, M. J. Buffo, J. Shogan, M. Anderson, J. M. Schroder, J. M. Wang, O. M. Howard, and J. J. Oppenheim. 1999. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286:525.PubMedCrossRefGoogle Scholar
  50. 50.
    Hewson, C. A., A. Jardine, M. R. Edwards, V. Laza-Stanca, and S. L. Johnston. 2005. Tolllike receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells. J Virol 79:12273.PubMedCrossRefGoogle Scholar
  51. 51.
    Wiehler, S., and D. Proud. 2007. Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection. Am J Physiol Lung Cell Mol Physiol 293:L505.PubMedCrossRefGoogle Scholar
  52. 52.
    Wark, P. A., S. L. Johnston, F. Bucchieri, R. Powell, S. Puddicombe, V. Laza-Stanca, S. T. Holgate, and D. E. Davies. 2005. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med 201:937.PubMedCrossRefGoogle Scholar
  53. 53.
    Contoli, M., S. D. Message, V. Laza-Stanca, M. R. Edwards, P. A. Wark, N. W. Bartlett, T. Kebadze, P. Mallia, L. A. Stanciu, H. L. Parker, L. Slater, A. Lewis-Antes, O. M. Kon, S. T. Holgate, D. E. Davies, S. V. Kotenko, A. Papi, and S. L. Johnston. 2006. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 12:1023.PubMedCrossRefGoogle Scholar
  54. 54.
    Sanders, S. P., E. S. Siekierski, S. M. Richards, J. D. Porter, F. Imani, and D. Proud. 2001. Rhinovirus infection induces expression of type 2 nitric oxide synthase in human respiratory epithelial cells in vitro and in vivo. J Allergy Clin Immunol 107:235.PubMedCrossRefGoogle Scholar
  55. 55.
    Schutte, B. C., and P. B. McCray, Jr. 2002. [beta]-defensins in lung host defense. Annu Rev Physiol 64:709.PubMedCrossRefGoogle Scholar
  56. 56.
    Biragyn, A., M. Surenhu, D. Yang, P. A. Ruffini, B. A. Haines, E. Klyushnenkova, J. J. Oppenheim, and L. W. Kwak. 2001. Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonim-munogenic tumor antigens. J Immunol 167:6644.PubMedGoogle Scholar
  57. 57.
    Biragyn, A., P. A. Ruffini, C. A. Leifer, E. Klyushnenkova, A. Shakhov, O. Chertov, A. K. Shirakawa, J. M. Farber, D. M. Segal, J. J. Oppenheim, and L. W. Kwak. 2002. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 298:1025.PubMedCrossRefGoogle Scholar
  58. 58.
    Proud, D., S. P. Sanders, and S. Wiehler. 2004. Human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. J Immunol 172:4637.PubMedGoogle Scholar
  59. 59.
    Alexopoulou, L., A. C. Holt, R. Medzhitov, and R. A. Flavell. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732.PubMedCrossRefGoogle Scholar
  60. 60.
    Yoneyama, M., M. Kikuchi, T. Natsukawa, N. Shinobu, T. Imaizumi, M. Miyagishi, K. Taira, S. Akira, and T. Fujita. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5:730.PubMedCrossRefGoogle Scholar
  61. 61.
    Kang, D. C., R. V. Gopalkrishnan, L. Lin, A. Randolph, K. Valerie, S. Pestka, and P. B. Fisher. 2004. Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene. Oncogene 23:1789.PubMedCrossRefGoogle Scholar
  62. 62.
    Kang, D. C., R. V. Gopalkrishnan, Q. Wu, E. Jankowsky, A. M. Pyle, and P. B. Fisher. 2002. mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci USA 99:637.PubMedCrossRefGoogle Scholar
  63. 63.
    Siren, J., T. Imaizumi, D. Sarkar, T. Pietila, D. L. Noah, R. Lin, J. Hiscott, R. M. Krug, P. B. Fisher, I. Julkunen, and S. Matikainen. 2006. Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines. Microbes Infect 8:2013.PubMedCrossRefGoogle Scholar
  64. 64.
    Sha, Q., A. Q. Truong-Tran, J. R. Plitt, L. A. Beck, and R. P. Schleimer. 2004. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol 31:358.PubMedCrossRefGoogle Scholar
  65. 65.
    Liu, P., M. Jamaluddin, K. Li, R. P. Garofalo, A. Casola, and A. R. Brasier. 2007. Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J Virol 81:1401.PubMedCrossRefGoogle Scholar
  66. 66.
    Guillot, L., R. Le Goffic, S. Bloch, N. Escriou, S. Akira, M. Chignard, and M. Si-Tahar. 2005. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 280:5571.PubMedCrossRefGoogle Scholar
  67. 67.
    Johnsen, I. B., T. T. Nguyen, M. Ringdal, A. M. Tryggestad, O. Bakke, E. Lien, T. Espevik, and M. W. Anthonsen. 2006. Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. Embo J 25:3335.PubMedCrossRefGoogle Scholar
  68. 68.
    Matsukura, S., F. Kokubu, M. Kurokawa, M. Kawaguchi, K. Ieki, H. Kuga, M. Odaka, S. Suzuki, S. Watanabe, H. Takeuchi, T. Kasama, and M. Adachi. 2006. Synthetic double-stranded RNA induces multiple genes related to inflammation through Toll-like receptor 3 depending on NF-kappaB and/or IRF-3 in airway epithelial cells. Clin Exp Allergy 36:1049.PubMedCrossRefGoogle Scholar
  69. 69.
    Niimi, K., K. Asano, Y. Shiraishi, T. Nakajima, M. Wakaki, J. Kagyo, T. Takihara, Y. Suzuki, K. Fukunaga, T. Shiomi, T. Oguma, K. Sayama, K. Yamaguchi, Y. Natori, M. Matsumoto, T. Seya, M. Yamaya, and A. Ishizaka. 2007. TLR3-mediated synthesis and release of eotaxin-1/ CCL11 from human bronchial smooth muscle cells stimulated with double-stranded RNA. J Immunol 178:489.PubMedGoogle Scholar
  70. 70.
    Garcia, M. A., J. Gil, I. Ventoso, S. Guerra, E. Domingo, C. Rivas, and M. Esteban. 2006. Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol Mol Biol Rev 70:1032.PubMedCrossRefGoogle Scholar
  71. 71.
    Garcia, M. A., E. F. Meurs, and M. Esteban. 2007. The dsRNA protein kinase PKR: virus and cell control. Biochimie 89:799.PubMedCrossRefGoogle Scholar
  72. 72.
    Chen, Y., E. Hamati, P. K. Lee, W. M. Lee, S. Wachi, D. Schnurr, S. Yagi, G. Dolganov, H. Boushey, P. Avila, and R. Wu. 2006. Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways. Am J Respir Cell Mol Biol 34:192.PubMedCrossRefGoogle Scholar
  73. 73.
    Matsukura, S., F. Kokubu, M. Kurokawa, M. Kawaguchi, K. Ieki, H. Kuga, M. Odaka, S. Suzuki, S. Watanabe, T. Homma, H. Takeuchi, K. Nohtomi, and M. Adachi. 2007. Role of RIG-I, MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic dsRNA in airway epithelial cells. Int Arch Allergy Immunol 143(Suppl 1):80.PubMedCrossRefGoogle Scholar
  74. 74.
    Gern, J. E., D. A. French, K. A. Grindle, R. A. Brockman-Schneider, S. Konno, and W. W. Busse. 2003. Double-stranded RNA induces the synthesis of specific chemokines by bronchial epithelial cells. Am J Respir Cell Mol Biol 28:731.PubMedCrossRefGoogle Scholar
  75. 75.
    Konno, S., K. A. Grindle, W. M. Lee, M. K. Schroth, A. G. Mosser, R. A. Brockman-Schneider, W. W. Busse, and J. E. Gern. 2002. Interferon-gamma enhances rhinovirus-induced RANTES secretion by airway epithelial cells. Am J Respir Cell Mol Biol 26:594.PubMedGoogle Scholar
  76. 76.
    Kato, A., S. Favoreto, Jr., P. C. Avila, and R. P. Schleimer. 2007. TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells. J Immunol 179:1080.PubMedGoogle Scholar
  77. 77.
    Kato, A., A. Q. Truong-Tran, A. L. Scott, K. Matsumoto, and R. P. Schleimer. 2006. Airway epithelial cells produce B cell-activating factor of TNF family by an IFN-beta-dependent mechanism. J Immunol 177:7164.PubMedGoogle Scholar
  78. 78.
    Zhu, Z., W. Tang, A. Ray, Y. Wu, O. Einarsson, M. L. Landry, J. Gwaltney, Jr., and J. A. Elias. 1996. Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation. J Clin Invest 97:421.PubMedCrossRefGoogle Scholar
  79. 79.
    Kim, J., S. P. Sanders, E. S. Siekierski, V. Casolaro, and D. Proud. 2000. Role of NF-kappa B in cytokine production induced from human airway epithelial cells by rhinovirus infection. J Immunol 165:3384.PubMedGoogle Scholar
  80. 80.
    Barnes, P. J., and M. Karin. 1997. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066.PubMedCrossRefGoogle Scholar
  81. 81.
    Funkhouser, A. W., J. A. Kang, A. Tan, J. Li, L. Zhou, M. K. Abe, J. Solway, and M. B. Hershenson. 2004. Rhinovirus 16 3C protease induces interleukin-8 and granulocyte-macrophage colony-stimulating factor expression in human bronchial epithelial cells. Pediatr Res 55:13.PubMedCrossRefGoogle Scholar
  82. 82.
    Papi, A., and S. L. Johnston. 1999. Respiratory epithelial cell expression of vascular cell adhesion molecule-1 and its up-regulation by rhinovirus infection via NF-kappaB and GATA transcription factors. J Biol Chem 274:30041.PubMedCrossRefGoogle Scholar
  83. 83.
    Ieki, K., S. Matsukura, F. Kokubu, T. Kimura, H. Kuga, M. Kawaguchi, M. Odaka, S. Suzuki, S. Watanabe, H. Takeuchi, R. P. Schleimer, and M. Adachi. 2004. Double-stranded RNA activates RANTES gene transcription through co-operation of nuclear factor-kappaB and interferon regulatory factors in human airway epithelial cells. Clin Exp Allergy 34:745.PubMedCrossRefGoogle Scholar
  84. 84.
    Suzuki, T., M. Yamaya, M. Kamanaka, Y. X. Jia, K. Nakayama, M. Hosoda, N. Yamada, H. Nishimura, K. Sekizawa, and H. Sasaki. 2001. Type 2 rhinovirus infection of cultured human tracheal epithelial cells: role of LDL receptor. Am J Physiol Lung Cell Mol Physiol 280:L409.PubMedGoogle Scholar
  85. 85.
    Einarsson, O., G. P. Geba, Z. Zhu, M. Landry, and J. A. Elias. 1996. Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness. J Clin Invest 97:915.PubMedCrossRefGoogle Scholar
  86. 86.
    Donninger, H., R. Glashoff, H. M. Haitchi, J. A. Syce, R. Ghildyal, E. van Rensburg, and P. G. Bardin. 2003. Rhinovirus induction of the CXC chemokine epithelial-neutrophil activating peptide-78 in bronchial epithelium. J Infect Dis 187:1809.PubMedCrossRefGoogle Scholar
  87. 87.
    Spurrell, J. C., S. Wiehler, R. S. Zaheer, S. P. Sanders, and D. Proud. 2005. Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection. Am J Physiol Lung Cell Mol Physiol 289:L85.PubMedCrossRefGoogle Scholar
  88. 88.
    Schroth, M. K., E. Grimm, P. Frindt, D. M. Galagan, S. I. Konno, R. Love, and J. E. Gern. 1999. Rhinovirus replication causes RANTES production in primary bronchial epithelial cells. Am J Respir Cell Mol Biol 20:1220.PubMedGoogle Scholar
  89. 89.
    Teran, L. M., M. C. Seminario, J. K. Shute, A. Papi, S. J. Compton, J. L. Low, G. J. Gleich, and S. L. Johnston. 1999. RANTES, macrophage-inhibitory protein 1alpha, and the eosi-nophil product major basic protein are released into upper respiratory secretions during virus-induced asthma exacerbations in children. J Infect Dis 179:677.PubMedCrossRefGoogle Scholar
  90. 90.
    Stellato, C., S. Matsukura, A. Fal, J. White, L. A. Beck, D. Proud, and R. P. Schleimer. 1999. Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glu-cocorticoid budesonide. J Immunol 163:5624.PubMedGoogle Scholar
  91. 91.
    Sanders, S. P., D. Proud, S. Permutt, E. S. Siekierski, R. Yachechko, and M. C. Liu. 2004. Role of nasal nitric oxide in the resolution of experimental rhinovirus infection. J Allergy Clin Immunol 113:697.PubMedCrossRefGoogle Scholar
  92. 92.
    Seymour, M. L., N. Gilby, P. G. Bardin, D. J. Fraenkel, G. Sanderson, J. F. Penrose, S. T. Holgate, S. L. Johnston, and A. P. Sampson. 2002. Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. J Infect Dis 185:540.PubMedCrossRefGoogle Scholar
  93. 93.
    Papi, A., G. Caramori, I. M. Adcock, and S. L. Johnston. 2003. Respiratory viral infections. Marcel Dekker, New York.Google Scholar
  94. 94.
    Duits, L. A., P. H. Nibbering, E. van Strijen, J. B. Vos, S. P. Mannesse-Lazeroms, M. A. van Sterkenburg, and P. S. Hiemstra. 2003. Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. FEMS Immunol Med Microbiol 38:59.PubMedCrossRefGoogle Scholar
  95. 95.
    Inoue, D., M. Yamaya, H. Kubo, T. Sasaki, M. Hosoda, M. Numasaki, Y. Tomioka, H. Yasuda, K. Sekizawa, H. Nishimura, and H. Sasaki. 2006. Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells. Respir Physiol Neurobiol 154:484.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Jean Kim
    • 1
  • Robert Schleimer
    • 2
  1. 1.Department of Otolaryngology, Head and Neck Surgery and Department of Medicine, Allergy and Clinical ImmunologyJohns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy CenterBaltimoreUSA
  2. 2.Chief, Allergy-ImmunologyNorthwestern Feinberg School of MedicineChicagoUSA

Personalised recommendations