Uteroglobin-related protein 1 (UGRP1), also named SCGB(secretoglobin)3A2, was originally identified as a downstream target gene for the homeodomain transcription factor T/EBP (thyroid-specific enhancer binding protein). UGRP1 is a homodimeric secretory protein of approximately 10 kDa and is highly expressed in epithelial cells of the trachea, bronchus and bronchioles. UGRP1 has an amino acid sequence similar to the Uteroglobin/Clara cell secretory protein, known to function as an anti-inflammatory agent. The UGRP1 gene is located on human chromosome 5q31-q32, a region where an asthma susceptibility locus has been assigned. Further, decreased Ugrp1 mRNA level was found in inflamed mouse lungs. All these suggested that UGRP1 may play a role in lung inflammation.? ? In order to understand the role of UGRP1 in lung inflammation, ovalbumin-sensitized and challenged mice, a model for allergic bronchial asthma, were used in conjunction with recombinant adenovirus expressing UGRP1. 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 tissues as well as the level of pro-inflammatory cytokines such as IL-4, 5, and 13 in bronchoalveolar lavage fluids. These results demonstrate that UGRP1 can suppress allergic airway inflammation in a mouse model of allergic bronchial asthma. It is believed that inflammation is involved in tumorigenesis. Experiments are planed to study the effect of UGRP1 in lung carcinogenesis using chemical carcinogenesis model mouse.? ? Another member of the SCGB gene superfamily, SCGB3A1 (UGRP2), closely related to UGRP1 in terms of amino acid sequence, has also been hypothesized to be involved in lung inflammation. The effect of various cytokines on the expression of UGRP2 was examined using mtCC cells that are derived from lung Clara cells of transgenic mice expressing the SV40 large T antigen. Ugrp2 mRNA expression was enhanced by IL-4 and IL-13 through STAT6 binding to the proximal STAT-binding element located in the Ugrp2 gene promoter. This finding is consistent with a potential role for this gene in the pathogenesis of inflammatory lung diseases such as asthma. Further studies to understand the effect of various cytokines on the expression of UGRP1 and UGRP2, and their mechanisms are in progress.?

National Institute of Health (NIH)
Division of Basic Sciences - NCI (NCI)
Intramural Research (Z01)
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