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Published ahead of print on February 2, 2006, doi:10.1164/rccm.200503-456OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 9, May 2006, 958-964

A more recent version of this article appeared on May 1, 2006
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Submitted on March 22, 2005
Accepted on January 27, 2006

Uteroglobin-related Protein 1 Expression Suppresses Allergic Airway Inflammation in Mice

Yoshihiko Chiba1, Reiko Kurotani2, Takashi Kusakabe3, Tomiko Miura3, Benjamin W Link4, Miwa Misawa5, and Shioko Kimura2*

1 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Pharmacology, Hoshi University, School of Pharmacy, Tokyo, Japan, 2 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, 3 Department of Pathology, Fukushima Medical University, Fukushima, Japan, 4 Science Applications International Corporation (SAIC), MD, USA, 5 Department of Pharmacology, Hoshi University, School of Pharmacy, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: shioko{at}helix.nih.gov.

Rationale: Uteroglobin-related protein (UGRP) 1 that is highly expressed in the epithelial cells of the airways has been suggested to play a role in lung inflammation. Objectives: The aim of study was to understand the effect of over-expressed UGRP1 on lung inflammation in a mouse model of allergic airway inflammation. Methods: Ovalbumin-sensitized and challenged mice, a model for allergic airway inflammation, were used in conjunction with recombinant adenovirus expressing UGRP1. Measurements and Main Results: We demonstrated that intranasal administration of adeno-UGRP1 successfully delivered UGRP1 to the epithelial cells of airways and markedly reduced the number of infiltrating inflammatory cells, particularly eosinophils in lung tissue as well as the level of pro-inflammatory cytokines such as IL-4, 5, and 13 in bronchoalveolar lavage fluids. The healed phase of inflammation was clearly seen in the peripheral areas of adeno-UGRP1-treated mouse lungs. Conclusion: These results demonstrate that UGRP1 can suppress inflammation in the mouse model of allergic airway inflammation. Based on this result, we propose UGRP1 as a novel therapeutic candidate for treating lung inflammation such as found in asthma.
Key words: mouse model, eosinophils, bronchoalveolar lavage, asthma, ovalbumin




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