| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print December 20, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00195.2001
Submitted on June 1, 2001
Accepted on December 2, 2001
1 Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
2 Pharmaceutical Division-Biotechnology, Bayer Corporation, Berkeley, CA, USA
* To whom correspondence should be addressed. E-mail: nlee{at}mayo.edu.
Goblet cell metaplasia/hyperplasia and mucus overproduction in the airway are common features of asthma, contributing to the narrowing of mid-sized airways and leading, in part, to the clinical manifestation of airway obstruction. Mouse models of allergic pulmonary inflammation have demonstrated that elaboration of IL-4/IL-13 levels in the lung by CD4+ T cells is causatively linked to this allergen-induced mucus overproduction. However, expression of IL-5, and an accompanying pulmonary eosinophilia, are also common features of asthma patients and the mouse models, potentially representing an alternative pathway leading to mucus overproduction. The potential role of airway IL-5 expression to elicit mucus production independent of allergen exposure was demonstrated in a pulmonary IL-5 transgenic mouse model (NJ.1726) in which naive transgenic mice display comparable levels of mucus production relative to allergen sensitized/aerosol challenged wild-type mice. Moreover, the intrinsic mucus production of NJ.1726 mice was abolished in compound transgenic-gene knockout mice deficient of either CD4+ cells (NJ.1726/CD4(-/-)) or 
ßTCR+ cells (NJ.1726/ßTCR(-/-)). In addition, mucus production in naive NJ.1726 mice was inhibited by >90% following the administration of IL-4 mutant protein receptor antagonist into the airways. The loss of mucus production occurred in these mice despite elevated levels of airway and peripheral IL-5, indicating that IL-5 does not directly induce goblet cell metaplasia and mucus production. Furthermore, the loss of mucus production in NJ.1726/CD4(-/-), NJ.1726/ßTCR(-/-), and IL-4 receptor antagonist-treated mice occurred despite a significant pulmonary eosinophilia and expansion of airway B cells induced by ectopic IL-5 expression. Thus, ectopic pulmonary expression of IL-5, independent of allergic inflammation, results in a CD4+ T cell-dependent goblet cell metaplasia apparently mediated by IL-4R-ligand interactions. This IL-5 mediated mechanism may represent a novel pathway for augmenting allergen-induced mucus production through previously unrecognized effector function(s) on T cells.
This article has been cited by other articles:
|
|
 |
|
  Z. Bao, S. Guan, C. Cheng, S. Wu, S. H. Wong, D. M. Kemeny, B. P. Leung, and W. S. F. Wong A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-{kappa}B Pathway Am. J. Respir. Crit. Care Med., April 15, 2009; 179(8): 657 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Bao, S. Lim, W. Liao, Y. Lin, C. Thiemermann, B. P. Leung, and W. S. F. Wong Glycogen Synthase Kinase-3beta Inhibition Attenuates Asthma in Mice Am. J. Respir. Crit. Care Med., September 1, 2007; 176(5): 431 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Buchweitz, J. R. Harkema, and N. E. Kaminski Time-Dependent Airway Epithelial and Inflammatory Cell Responses Induced by Influenza Virus A/PR/8/34 in C57BL/6 Mice Toxicol Pathol, April 1, 2007; 35(3): 424 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. S. George, M. L. White, K. Kulhankova, A. Mahajan, P. S. Thorne, J. M. Snyder, and J. N. Kline Early exposure to a nonhygienic environment alters pulmonary immunity and allergic responses Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L512 - L522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Duan, J. H. P. Chan, K. McKay, J. R. Crosby, H. H. Choo, B. P. Leung, J. G. Karras, and W. S. F. Wong Inhaled p38{alpha} Mitogen-activated Protein Kinase Antisense Oligonucleotide Attenuates Asthma in Mice Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 571 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Voynow, B. M. Fischer, D. E. Malarkey, L. H. Burch, T. Wong, M. Longphre, S. B. Ho, and W. M. Foster Neutrophil elastase induces mucus cell metaplasia in mouse lung Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1293 - L1302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Duan, J. H. P. Chan, C. H. Wong, B. P. Leung, and W. S. F. Wong Anti-Inflammatory Effects of Mitogen-Activated Protein Kinase Kinase Inhibitor U0126 in an Asthma Mouse Model J. Immunol., June 1, 2004; 172(11): 7053 - 7059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Shen, S. I. Ochkur, M. P. McGarry, J. R. Crosby, E. M. Hines, M. T. Borchers, H. Wang, T. L. Biechelle, K. R. O'Neill, T. L. Ansay, et al. A Causative Relationship Exists Between Eosinophils and the Development of Allergic Pulmonary Pathologies in the Mouse J. Immunol., March 15, 2003; 170(6): 3296 - 3305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Perez-Vilar, J. K. Sheehan, and S. H. Randell Making More MUCS Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 267 - 270. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
