| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Perinatal Medicine, Yale University School of Medicine, Department of Pediatrics, Children’s Hospital, New Haven, CT 06520;
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, Department of Internal Medicine, New Haven, CT 06520; and
Yale University School of Medicine, Department of Pathology, New Haven, CT 06520
IL-13 is a critical effector at sites of Th2 inflammation and remodeling. As a result, anti-IL-13-based therapies are being actively developed to treat a variety of diseases and disorders. However, the beneficial effects of endogenous IL-13 in the normal and diseased lung have not been adequately defined. We hypothesized that endogenous IL-13 is an important regulator of oxidant-induced lung injury and inflammation. To test this hypothesis, we compared the effects of 100% O2 in mice with wild-type and null IL-13 loci. In this study, we demonstrate that hyperoxia significantly augments the expression of the components of the IL-13R, IL-13R
1, and IL-4R. We also demonstrate that, in the absence of IL-13, hyperoxia-induced tissue inflammation is decreased. In contrast, in the IL-13 null mice, DNA injury, cell death, caspase expression, and activation and mortality are augmented. Interestingly, the levels of the cytoprotective cytokines vascular endothelial cell growth factor, IL-6, and IL-11 were decreased in the bronchoalveolar lavage fluid. These studies demonstrate that the expression of the IL-13R is augmented and that the endogenous IL-13-IL-13R pathway contributes to the induction of inflammation and the inhibition of injury in hyperoxic acute lung injury.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported in part by Grants HL-74195 (to V.B.), HL-64642, HL-61904, and HL-56389 (to J.A.E.) from the National Heart, Lung, and Blood Institute of the National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Jack A. Elias, Yale University School of Medicine, Department of Internal Medicine, 1 Gilbert Street, New Haven, CT 06520. E-mail address: jack.elias{at}yale.edu
3 Abbreviations used in this paper: IPF, idiopathic pulmonary fibrosis; ROS, reactive oxidant species; HALI, hyperoxic acute lung injury; WT, wild type; BAL, bronchoalveolar lavage; PKC, protein kinase C; BCIP, 5-bromo-4-chloro-3'-indolyphosphate p-toluidine salt; FasL, Fas ligand.
This article has been cited by other articles:
|
|
 |
|
  D. R. Prows, A. V. Winterberg, W. J. Gibbons Jr., B. B. Burzynski, C. Liu, and T. G. Nick Reciprocal backcross mice confirm major loci linked to hyperoxic acute lung injury survival time Physiol Genomics, July 1, 2009; 38(2): 158 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Murray, D. A. Knight, L. McAlonan, R. Argentieri, A. Joshi, F. Shaheen, M. Cunningham, L. Alexopolou, R. A. Flavell, R. T. Sarisky, et al. Deleterious Role of TLR3 during Hyperoxia-induced Acute Lung Injury Am. J. Respir. Crit. Care Med., December 15, 2008; 178(12): 1227 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bhandari, R. Choo-Wing, C. G. Lee, K. Yusuf, J. H. Nedrelow, N. Ambalavanan, H. Malkus, R. J. Homer, and J. A. Elias Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 420 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Lavoie, C. Pham, and K. L. Jang Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health Pediatrics, September 1, 2008; 122(3): 479 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Matute-Bello, C. W. Frevert, and T. R. Martin Animal models of acute lung injury Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L379 - L399. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
