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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ckless, K. Articles by Janssen-Heininger, Y. M. W. Search for Related Content PubMed PubMed Citation Articles by Ckless, K. Articles by Janssen-Heininger, Y. M. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB L-TYROSINE NITRIC OXIDE

Inhibition of Arginase Activity Enhances Inflammation in Mice with Allergic Airway Disease, in Association with Increases in Protein S-Nitrosylation and Tyrosine Nitration¹

Karina Ckless^*, Anniek Lampert^*, Jessica Reiss^*, David Kasahara^*, Matthew E. Poynter, Charles G. Irvin, Lennart K. A. Lundblad, Ryan Norton, Albert van der Vliet^* and Yvonne M. W. Janssen-Heininger^2,*

^* Department of Pathology, and Department of Medicine, University of Vermont, Burlington, VT 05405

Pulmonary inflammation in asthma is orchestrated by the activity of NF-B. NO and NO synthase (NOS) activity are important modulators of inflammation. The availability of the NOS substrate, L-arginine, is one of the mechanisms that controls the activity of NOS. Arginase also uses L-arginine as its substrate, and arginase-1 expression is highly induced in a murine model of asthma. Because we have previously described that arginase affects NOx content and interferes with the activation of NF-B in lung epithelial cells, the goal of this study was to investigate the impact of arginase inhibition on the bioavailability of NO and the implications for NF-B activation and inflammation in a mouse model of allergic airway disease. Administration of the arginase inhibitor BEC (S-(2-boronoethyl)-L-cysteine) decreased arginase activity and caused alterations in NO homeostasis, which were reflected by increases in S-nitrosylated and nitrated proteins in the lungs from inflamed mice. In contrast to our expectations, BEC enhanced perivascular and peribronchiolar lung inflammation, mucus metaplasia, NF-B DNA binding, and mRNA expression of the NF-B-driven chemokine genes CCL20 and KC, and lead to further increases in airways hyperresponsiveness. These results suggest that inhibition of arginase activity enhanced a variety of parameters relevant to allergic airways disease, possibly by altering NO homeostasis.

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 work was supported by Grants RO1 HL60014 and HL074295 from the National Institutes of Health.

² Address correspondence and reprint requests to Yvonne Janssen-Heininger, Department of Pathology, Health Sciences Research Facility, Room 216A, University of Vermont, Burlington VT 05405. E-mail address: yvonne.janssen{at}uvm.edu

³ Abbreviations used in this paper: iNOS, inducible NO synthase; NOS, NO synthase; RNS, reactive nitrogen species; BAL, bronchoalveolar lavage.

This article has been cited by other articles:

				H. Maarsingh, B. E. Bossenga, I. S. T. Bos, H. H. Volders, J. Zaagsma, and H. Meurs L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction Eur. Respir. J., July 1, 2009; 34(1): 191 - 199. [Abstract] [Full Text] [PDF]

				M. L. North, N. Khanna, P. A. Marsden, H. Grasemann, and J. A. Scott Functionally important role for arginase 1 in the airway hyperresponsiveness of asthma Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L911 - L920. [Abstract] [Full Text] [PDF]