Sec14l3 is specifically expressed in mouse airway ciliated cells.

Airway epithelium is a key component for airway integrity. Previously, we found that expression of the Sec14l3 gene that encodes a 45-kDa secretory protein is inversely associated with the progression of experimentally induced airway inflammation and degeneration/necrosis of alveolar epithelium. In this report, using in situ hybridization we demonstrated that the ciliated cells in mouse lung selectively express Sec14l3 mRNA. In a three-dimensional culture of mouse tracheal epithelial cells, levels of the Sec14l3 mRNA correlated with the differentiation of ciliated cells. Intranasal infection of adult mice with influenza virus resulted in a 20-fold, progressive decrease in Sec14l3 mRNA expression over 10 days post infection. These results enhance the potential value of Sec14l3 as a ciliated epithelial cell-specific biomarker for the progression of airway inflammations such as airway viral infection and asthma.

Inverse relationship between Sec14l3 mRNA/protein expression and allergic airway inflammation.

Bronchial asthma is an inflammatory disease of the airways. The Sec14l3 gene, encoding a 45-kDa secretory protein, is specifically expressed in airway epithelium. Here, we report on the kinetics of Sec14l3 expression following allergic inflammation of the lung. Brown Norway rats were sensitized by intraperitoneal injection of ovalbumin, followed by challenge with aerosolized ovalbumin after a 3-week interval. This animal model showed many features similar to human allergic asthma: an increase in inflammatory cells such as eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid and histopathological alteration of lung tissue, exhibiting infiltration of these inflammatory cells and degeneration and necrosis of alveolar epithelium. These parameters reached their maximal level 24h after allergen challenge. In contrast, quantitative polymerase chain reaction analyses demonstrated a rapid and significant reduction of Sec14l3 mRNA in lung tissue and maximum reduction (to 1.4% of the control) was observed at 24h. Pretreatment with dexamethasone significantly suppressed both the Sec14I3 mRNA reduction and all of the inflammatory changes. The 45-kDa secretory protein was identified in the supernatant of BAL fluids. Two-dimensional gel images of the supernatant proteome also revealed down-regulation of the protein following inflammation (to approximately 30% of the control at 24h). Thus, Sec14l3 expression is highly and inversely associated with the progression of airway inflammation. Sec14l3 mRNA and protein may function in the homeostasis of airway epithelial cells under normal conditions.

Pulmonary inflammation in brown Norway rats: possible association of environmental particles in the animal room environment.

Brown Norway (BN) rats have been found to develop granulomatous pneumonia with high spontaneous incidence under normal husbandry conditions. In our laboratory, ambient particles from the animal housing environment were suspected to be involved in the pathogenesis of these pulmonary lesions. In the present study, we correlated the histopathology of spontaneous granulomatous pneumonia with the cytology of bronchoalveolar lavage fluid (BALF) analysis and animal room particle counts. The results show that the sum of the macroscopic lesion score in the lung correlated with the number of eosinophils in the BALF. Microscopically, the severity of granulomatous lesions was significantly correlated with both pulmonary eosinophils and the number of eosinophils in the BALF, but not with those of neutrophils or lymphocytes. In addition, the histological features of the lesions were not influenced by housing conditions or sensitization with ovalbumin. Ambient particles (0.3-1.0 microm in diameter) in the animal room environment were measured and compared with the number of eosinophils in BALF. Interestingly, there was a significant correlation between them, suggesting a possible relationship between environmental particles and the pathogenesis of granulomatous pneumonia in BN rats. However, further study is needed to clarify the pathogenic mechanism.