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

Laboratory of Metabolism, National Cancer Institute, National Institutes of Health; Science Applications International Corporation, Bethesda, Maryland; Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo; and Department of Pathology, Fukushima Medical University, Fukushima, Japan

Correspondence and requests for reprints should be addressed to Shioko Kimura, Ph.D., Bldg. 37, Rm. 3112B, National Institutes of Health, Bethesda, MD 20892. E-mail: shioko{at}helix.nih.gov

Rationale: Uteroglobin-related protein (UGRP) 1, which 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 overexpressed 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 proinflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-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 is found in asthma.

Key Words: asthma • bronchoalveolar lavage • eosinophils • mouse model • ovalbumin

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