| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
, But Not Fas, Mediates Reduction of Allergen-Induced Mucous Cell Metaplasia by Inducing Apoptosis
* Lovelace Respiratory Research Institute, and
Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87108; and
Aventis Pharmaceutical, Inc., Bridgewater, NJ 08870.
Inflammatory responses induced by allergen exposure cause mucous
cell metaplasia (MCM) by differentiation of existing and proliferating
epithelial cells into mucus-storing cells. Airway epithelia have
various mechanisms that resolve these changes to form normal airway
epithelia. In this report, we first investigated the state of mucous
cell metaplasia and the mechanisms by which MCM is reduced despite
continued exposures to allergen. After 5 days of allergen exposure,
extensive MCM had developed but was reduced when allergen challenge was
continued for 15 days. During this exposure period, IL-13 levels
decreased and IFN-
levels increased in the bronchoalveolar lavage
fluid. In contrast, IL-13 levels decreased but IFN- was not detected
at any time point during the resolution of MCM following cessation of
allergen exposure. Instillation of IFN- but not anti-Fas caused
accelerated resolution of MCM and MCM was not resolved in
Stat1-deficient mice exposed to allergen for 15 days, confirming that
IFN- is crucial for reducing MCM during prolonged exposures to
allergen. IFN- but not anti-Fas induced apoptotic cell death in
proliferating normal human bronchial epithelial cells and in human
bronchial epithelial cells from subjects with asthma. The apoptotic
effect of IFN- was caspase dependent and was inhibited by IL-13,
indicating that the Th2 milieu in asthmatics may maintain MCM by
preventing cell death in metaplastic mucous cells. These studies could
be useful in the understanding of deficiencies leading to chronicity in
airway changes and designing novel therapies to reverse MCM and airway
obstruction in asthmatics.
This article has been cited by other articles:
|
|
 |
|
  Y. A. Mebratu, B. F. Dickey, C. Evans, and Y. Tesfaigzi The BH3-only protein Bik/Blk/Nbk inhibits nuclear translocation of activated ERK1/2 to mediate IFN{gamma}-induced cell death J. Cell Biol., November 3, 2008; 183(3): 429 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Schwalm, J. F. Stevens, Z. Jiang, M. R. Schuyler, R. Schrader, S. H. Randell, F. H. Y. Green, and Y. Tesfaigzi Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1102 - L1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xiang, J. Rir-Sim-Ah, and Y. Tesfaigzi IL-9 and IL-13 Induce Mucous Cell Metaplasia That Is Reduced by IFN-{gamma} in a Bax-Mediated Pathway Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Stout, K. Melendez, J. Seagrave, M. J. Holtzman, B. Wilson, J. Xiang, and Y. Tesfaigzi STAT1 Activation Causes Translocation of Bax to the Endoplasmic Reticulum during the Resolution of Airway Mucous Cell Hyperplasia by IFN-{gamma} J. Immunol., June 15, 2007; 178(12): 8107 - 8116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wu, R. J. Martin, J. G. Rino, S. Jeyaseelan, R. Breed, and H. W. Chu A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1064 - L1072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pierce, J. Rir-Sima-Ah, I. Estrada, J. Wilder, A. Strasser, and Y. Tesfaigzi Loss of pro-apoptotic Bim promotes accumulation of pulmonary T lymphocytes and enhances allergen-induced goblet cell metaplasia Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L862 - L870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tesfaigzi Roles of Apoptosis in Airway Epithelia Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 537 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Phaybouth, S.-Z. Wang, J. A. Hutt, J. D. McDonald, K. S. Harrod, and E. G. Barrett Cigarette smoke suppresses Th1 cytokine production and increases RSV expression in a neonatal model Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L222 - L231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Rose and J. A. Voynow Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease Physiol Rev, January 1, 2006; 86(1): 245 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Harris, M. J. Fischer, J. R. Hotchkiss, B. P. Monia, S. H. Randell, J. R. Harkema, and Y. Tesfaigzi Bcl-2 Sustains Increased Mucous and Epithelial Cell Numbers in Metaplastic Airway Epithelium Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 764 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Evans, O. W. Williams, M. J. Tuvim, R. Nigam, G. P. Mixides, M. R. Blackburn, F. J. DeMayo, A. R. Burns, C. Smith, S. D. Reynolds, et al. Mucin Is Produced by Clara Cells in the Proximal Airways of Antigen-Challenged Mice Am. J. Respir. Cell Mol. Biol., October 1, 2004; 31(4): 382 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. Chu, S. Balzar, G. J. Seedorf, J. Y. Westcott, J. B. Trudeau, P. Silkoff, and S. E. Wenzel Transforming Growth Factor-{beta}2 Induces Bronchial Epithelial Mucin Expression in Asthma Am. J. Pathol., October 1, 2004; 165(4): 1097 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sehra, G. Pynaert, K. Tournoy, A. Haegeman, P. Matthys, Y. Tagawa, R. Pauwels, and J. Grooten Airway IgG Counteracts Specific and Bystander Allergen-Triggered Pulmonary Inflammation by a Mechanism Dependent on Fc{gamma}R and IFN-{gamma} J. Immunol., August 15, 2003; 171(4): 2080 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Foster, K. Gott, M. R. Schuyler, W. Kozak, and Y. Tesfaigzi LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L405 - L414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Harrod, R. J. Jaramillo, C. L. Rosenberger, S.-Z. Wang, J. A. Berger, J. D. McDonald, and M. D. Reed Increased Susceptibility to RSV Infection by Exposure to Inhaled Diesel Engine Emissions Am. J. Respir. Cell Mol. Biol., April 1, 2003; 28(4): 451 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tesfaigzi, M. J. Fischer, M. Daheshia, F. H. Y. Green, G. T. De Sanctis, and J. A. Wilder Bax is Crucial for IFN-{gamma}-Induced Resolution of Allergen- Induced Mucus Cell Metaplasia J. Immunol., November 15, 2002; 169(10): 5919 - 5925. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
