| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Pediatrics and
Pathology, University of Michigan Medical School, Ann Arbor, MI 48109; and
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109; and Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202
Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10–12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV-induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6-/- mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6-/- mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  S. S. Mohapatra and S. Boyapalle Epidemiologic, Experimental, and Clinical Links between Respiratory Syncytial Virus Infection and Asthma Clin. Microbiol. Rev., July 1, 2008; 21(3): 495 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Castilow, D. K. Meyerholz, and S. M. Varga IL-13 Is Required for Eosinophil Entry into the Lung during Respiratory Syncytial Virus Vaccine-Enhanced Disease J. Immunol., February 15, 2008; 180(4): 2376 - 2384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Smit, L. Boon, and N. W. Lukacs Respiratory Virus-Induced Regulation of Asthma-Like Responses in Mice Depends upon CD8 T Cells and Interferon-{gamma} Production Am. J. Pathol., December 1, 2007; 171(6): 1944 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Schaller, R. Neupane, B. D. Rudd, S. L. Kunkel, L. E. Kallal, P. Lincoln, J. B. Lowe, Y. Man, and N. W. Lukacs Notch ligand Delta-like 4 regulates disease pathogenesis during respiratory viral infections by modulating Th2 cytokines J. Exp. Med., November 26, 2007; 204(12): 2925 - 2934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. N. Gomperts, L. J. Kim, S. A. Flaherty, and B. P. Hackett IL-13 Regulates Cilia Loss and foxj1 Expression in Human Airway Epithelium Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 339 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Rudd, M. A. Schaller, J. J. Smit, S. L. Kunkel, R. Neupane, L. Kelley, A. A. Berlin, and N. W. Lukacs MyD88-Mediated Instructive Signals in Dendritic Cells Regulate Pulmonary Immune Responses during Respiratory Virus Infection J. Immunol., May 1, 2007; 178(9): 5820 - 5827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Singh, P. E. Moore, J. E. Gern, R. F. Lemanske Jr., and T. V. Hartert Bronchiolitis to Asthma: A Review and Call for Studies of Gene-Virus Interactions in Asthma Causation Am. J. Respir. Crit. Care Med., January 15, 2007; 175(2): 108 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Keane, B. N. Gomperts, S. Weigt, Y. Y. Xue, M. D. Burdick, H. Nakamura, D. A. Zisman, A. Ardehali, R. Saggar, J. P. Lynch III, et al. IL-13 Is Pivotal in the Fibro-Obliterative Process of Bronchiolitis Obliterans Syndrome J. Immunol., January 1, 2007; 178(1): 511 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Lukacs, M. L. Moore, B. D. Rudd, A. A. Berlin, R. D. Collins, S. J. Olson, S. B. Ho, and R. S. Peebles Jr Differential Immune Responses and Pulmonary Pathophysiology Are Induced by Two Different Strains of Respiratory Syncytial Virus Am. J. Pathol., September 1, 2006; 169(3): 977 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Smit, B. D. Rudd, and N. W. Lukacs Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus J. Exp. Med., May 15, 2006; 203(5): 1153 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Z. Wang, Y.-X. Bao, C. L. Rosenberger, Y. Tesfaigzi, J. M. Stark, and K. S. Harrod IL-12p40 and IL-18 Modulate Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection J. Immunol., September 15, 2004; 173(6): 4040 - 4049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Land, J. S. Moll, M. H. Kaplan, and G. S. Seetharamaiah Signal Transducer and Activator of Transcription (Stat)-6-Dependent, But Not Stat4-Dependent, Immunity Is Required for the Development of Autoimmunity in Graves' Hyperthyroidism Endocrinology, August 1, 2004; 145(8): 3724 - 3730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hashimoto, B. S. Graham, S. B. Ho, K. B. Adler, R. D. Collins, S. J. Olson, W. Zhou, T. Suzutani, P. W. Jones, K. Goleniewska, et al. Respiratory Syncytial Virus in Allergic Lung Inflammation Increases Muc5ac and Gob-5 Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 306 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Peng, T. Matsuda, and S. J. Hirst Signaling Pathways Regulating Interleukin-13-stimulated Chemokine Release from Airway Smooth Muscle Am. J. Respir. Crit. Care Med., March 1, 2004; 169(5): 596 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Z. Wang, C. L. Rosenberger, Y.-X. Bao, J. M. Stark, and K. S. Harrod Clara Cell Secretory Protein Modulates Lung Inflammatory and Immune Responses to Respiratory Syncytial Virus Infection J. Immunol., July 15, 2003; 171(2): 1051 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Raman, M. H. Kaplan, C. M. Hogaboam, A. Berlin, and N. W. Lukacs STAT4 Signal Pathways Regulate Inflammation and Airway Physiology Changes in Allergic Airway Inflammation Locally Via Alteration of Chemokines J. Immunol., April 1, 2003; 170(7): 3859 - 3865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Miller, R. M. Strieter, A. D. Gruber, S. B. Ho, and N. W. Lukacs CXCR2 Regulates Respiratory Syncytial Virus-Induced Airway Hyperreactivity and Mucus Overproduction J. Immunol., March 15, 2003; 170(6): 3348 - 3356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kondo, J. Tamaoki, K. Takeyama, J. Nakata, and A. Nagai Interleukin-13 Induces Goblet Cell Differentiation in Primary Cell Culture from Guinea Pig Tracheal Epithelium Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 536 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Wong, P. S. Foster, S. Yasuda, J. C. Qi, S. Mahalingam, E. A. Mellor, G. Katsoulotos, L. Li, J. A. Boyce, S. A. Krilis, et al. Biochemical and Functional Characterization of Human Transmembrane Tryptase (TMT)/Tryptase gamma . TMT IS AN EXOCYTOSED MAST CELL PROTEASE THAT INDUCES AIRWAY HYPERRESPONSIVENESS IN VIVO VIA AN INTERLEUKIN-13/INTERLEUKIN-4 RECEPTOR alpha /SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) 6-DEPENDENT PATHWAY J. Biol. Chem., October 25, 2002; 277(44): 41906 - 41915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-C. Chang, S. Zhang, and M. H. Kaplan Neonatal Tolerance in the Absence of Stat4- and Stat6- Dependent Th Cell Differentiation J. Immunol., October 15, 2002; 169(8): 4124 - 4128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. de Swart, T. Kuiken, H. H. Timmerman, G. v. Amerongen, B. G. van den Hoogen, H. W. Vos, H. J. Neijens, A. C. Andeweg, and A. D. M. E. Osterhaus Immunization of Macaques with Formalin-Inactivated Respiratory Syncytial Virus (RSV) Induces Interleukin-13-Associated Hypersensitivity to Subsequent RSV Infection J. Virol., October 11, 2002; 76(22): 11561 - 11569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chen, K.-F. Hu, B. Rozell, C. Orvell, B. Morein, and P. Liljestrom Vaccination with Recombinant Alphavirus or Immune-Stimulating Complex Antigen Against Respiratory Syncytial Virus J. Immunol., September 15, 2002; 169(6): 3208 - 3216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Duetsch, T. Illig, S. Loesgen, K. Rohde, N. Klopp, N. Herbon, H. Gohlke, J. Altmueller, and M. Wjst STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study Hum. Mol. Genet., March 1, 2002; 11(6): 613 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Walter, J. J. McIntire, G. Berry, A. N. J. McKenzie, D. D. Donaldson, R. H. DeKruyff, and D. T. Umetsu Critical Role for IL-13 in the Development of Allergen-Induced Airway Hyperreactivity J. Immunol., October 15, 2001; 167(8): 4668 - 4675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Tekkanat, H. Maassab, A. A. Berlin, P. M. Lincoln, H. L. Evanoff, M. H. Kaplan, and N. W. Lukacs Role of Interleukin-12 and Stat-4 in the Regulation of Airway Inflammation and Hyperreactivity in Respiratory Syncytial Virus Infection Am. J. Pathol., August 1, 2001; 159(2): 631 - 638. [Abstract] [Full Text]
|
|
|
|
|
|
N. W. Lukacs, K. K. Tekkanat, A. Berlin, C. M. Hogaboam, A. Miller, H. Evanoff, P. Lincoln, and H. Maassab Respiratory Syncytial Virus Predisposes Mice to Augmented Allergic Airway Responses Via IL-13-Mediated Mechanisms J. Immunol., July 15, 2001; 167(2): 1060 - 1065. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
