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: 289/1/L144    most recent 00348.2004v1 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 (6) Citing Articles via Google Scholar Google Scholar Articles by Stapleton, C. M. Articles by Jetten, A. M. Search for Related Content PubMed PubMed Citation Articles by Stapleton, C. M. Articles by Jetten, A. M.

Enhanced susceptibility of staggerer (ROR^sg/sg) mice to lipopolysaccharide-induced lung inflammation

Division of Intramural Research, Laboratory of Respiratory Biology, ¹Cell Biology Section and ³Molecular and Cellular Biology Section, ²Laboratory of Pathology, and ⁴Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina

Submitted 16 September 2004 ; accepted in final form 14 March 2005

The retinoid-related orphan receptor (ROR), a member of the ROR subfamily of nuclear receptors, has been implicated in the control of a number of physiological processes, including the regulation of several immune functions. To study the potential role of ROR in the regulation of innate immune responses in vivo, we analyzed the induction of airway inflammation in response to lipopolysaccharide (LPS) challenge in wild-type and staggerer (ROR^sg/sg) mice, a natural mutant strain lacking ROR expression. Examination of hematoxylin and eosin-stained lung sections showed that ROR^sg/sg mice displayed a higher degree of LPS-induced inflammation than wild-type mice. Bronchoalveolar lavage (BAL) was performed at 3, 16, and 24 h after LPS exposure to monitor the increase in inflammatory cells and the level of several cytokines/chemokines. The increased susceptibility of ROR^sg/sg mice to LPS-induced airway inflammation correlated with a higher number of total cells and neutrophils in BAL fluids from LPS-treated ROR^sg/sg mice compared with those from LPS-treated wild-type mice. In addition, IL-1, IL-6, and macrophage inflammatory protein-2 were appreciably more elevated in BAL fluids from LPS-treated ROR^sg/sg mice compared with those from LPS-treated wild-type mice. The enhanced susceptibility of ROR^sg/sg mice appeared not to be due to a repression of IB expression. Our observations indicate that ROR^sg/sg mice are more susceptible to LPS-induced airway inflammation and are in agreement with the hypothesis that ROR functions as a negative regulator of LPS-induced inflammatory responses.

retinoid-related orphan receptor ; innate immune response; nuclear receptor

This article has been cited by other articles:

				H. S. Kang, M. Angers, J. Y. Beak, X. Wu, J. M. Gimble, T. Wada, W. Xie, J. B. Collins, S. F. Grissom, and A. M. Jetten Gene expression profiling reveals a regulatory role for ROR{alpha} and ROR{gamma} in phase I and phase II metabolism Physiol Genomics, October 19, 2007; 31(2): 281 - 294. [Abstract] [Full Text] [PDF]

				M. Jaradat, C. Stapleton, S. L. Tilley, D. Dixon, C. J. Erikson, J. G. McCaskill, H. S. Kang, M. Angers, G. Liao, J. Collins, et al. Modulatory Role for Retinoid-related Orphan Receptor {alpha} in Allergen-induced Lung Inflammation Am. J. Respir. Crit. Care Med., December 15, 2006; 174(12): 1299 - 1309. [Abstract] [Full Text] [PDF]