HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/L105    most recent 00221.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Hartney, J. M. Articles by Koller, B. H. Search for Related Content PubMed PubMed Citation Articles by Hartney, J. M. Articles by Koller, B. H.

Prostaglandin E₂ protects lower airways against bronchoconstriction

¹Curriculum in Genetics and Molecular Biology, ²Department of Genetics, and ³Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, North Carolina; and ⁴Department of Pharmacology, Merck Frosst Canada, Kirkland, Quebec, Canada

Submitted 19 May 2005 ; accepted in final form 5 August 2005

Prostaglandin E₂ (PGE₂), similar to -adrenergic receptor agonists, can protect airways from bronchoconstriction and resulting increase in airway resistance induced by a number of agents, including cholinergic receptor agonists and antigen. We examined the impact of sustained alterations in PGE₂ pathways on changes in airway resistance. Genetic methods were utilized to alter PGE₂ metabolism and signal transduction in the murine lung. PGE₂ levels were elevated by generating mice lacking 15-hydroxyprostaglandin (Hpgd^–/–), the major catabolic enzyme of PGE₂, and by generating a transgenic line in which mouse PGE₂ synthase (Ptges) expression is driven by a human lung-specific promoter, hSP-C. Conversely, to determine the impact of loss of PGE₂ on airway reactivity, we examined mice lacking this synthase (Ptges^–/–) and receptors that mediate the actions of PGE₂, particularly the PGE₂ EP₂ receptor (Ptger2). Diminished capacity to produce and respond to PGE₂ did not alter the response of mice to cholinergic stimuli. In contrast, the responsiveness to cholinergic stimulation was dramatically altered in animals with elevated PGE₂ levels. The Hpgd^–/– and hSP-C-Ptges transgenic lines both showed attenuated airway responsiveness to methacholine as measured by lung resistance. Thus, whereas compromise of the Ptges/PGE₂/Ptger2 pathway does not alter airway responsiveness, genetic modulation that elevates PGE₂ levels in the lung attenuates airway responsiveness.

lung mechanics; bronchoprotection; prostaglandins; asthma; Ptges; Ptger2; 15-hydroxyprostaglandin

This article has been cited by other articles:

				M. A. Mall, J. R. Harkema, J. B. Trojanek, D. Treis, A. Livraghi, S. Schubert, Z. Zhou, S. M. Kreda, S. L. Tilley, E. J. Hudson, et al. Development of Chronic Bronchitis and Emphysema in {beta}-Epithelial Na+ Channel-Overexpressing Mice Am. J. Respir. Crit. Care Med., April 1, 2008; 177(7): 730 - 742. [Abstract] [Full Text] [PDF]

				G. L. Larsen, J. Loader, C. Fratelli, J.-k. B. Kang, A. Dakhama, and G. N. Colasurdo Modulation of airway responses by prostaglandins in young and fully grown rabbits Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L239 - L244. [Abstract] [Full Text] [PDF]

				P. D. N'Guessan, M. O. Etouem, B. Schmeck, A. C. Hocke, S. Scharf, K. Vardarova, B. Opitz, A. Flieger, N. Suttorp, and S. Hippenstiel Legionella pneumophila-induced PKC{alpha}-, MAPK-, and NF-{kappa}B-dependent COX-2 expression in human lung epithelium Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L267 - L277. [Abstract] [Full Text] [PDF]

				A. K. Lovgren, L. A. Jania, J. M. Hartney, K. K. Parsons, L. P. Audoly, G. A. FitzGerald, S. L. Tilley, and B. H. Koller COX-2-derived prostacyclin protects against bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L144 - L156. [Abstract] [Full Text] [PDF]

				P. D. N'Guessan, S. Hippenstiel, M. O. Etouem, J. Zahlten, W. Beermann, D. Lindner, B. Opitz, M. Witzenrath, S. Rosseau, N. Suttorp, et al. Streptococcus pneumoniae induced p38 MAPK- and NF-{kappa}B-dependent COX-2 expression in human lung epithelium Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1131 - L1138. [Abstract] [Full Text] [PDF]