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A7174 - The Effect of Corticosteroids and Long-Acting β2 Agonists on Airway Epithelial Barrier Dysfunction Induced by Cigarette Smoke and Incense Smoke
Author Block: M. Tatsuta, Y. Ishii, K. Kan-o, K. Matsumoto, A. Enokizu, A. Fujita, K. Tamura, S. Fukuyama, Y. Nakanishi; Research Institute for Diseases of the Chest Graduate School of Medical Sciences Kyushu University, Fukuoka, Japan.
RATIONALE: Indoor air pollution remains major challenge to the respiratory system worldwide. In Asian countries, many people burn incense daily when they worship at their homes and Buddhist temples. Previous studies suggested that cigarette smoke exposure leads to impairment of airway epithelial barrier. Corticosteroid is reported to have protective effects on cigarette smoke extract (CSE)-induced barrier dysfunction. However, association between incense smoke and epithelial barrier function is unknown. Long-acting β2 agonist (LABA) in addition to corticosteroid are reported to have synergistic effects on various impairment in airway diseases. We assessed effects of those indoor air pollutants on epithelial barrier function and examined whether or not corticosteroid plus LABA protects epithelial barrier function. METHODS: Human airway epithelial cell line, Calu-3 cells, were prepared using air-liquid interface method. The confluent cells were pretreated with corticosteroids (fluticasone or budesonide), and/or LABA (salmeterol or formoterol) for 2 h, and then stimulated with CSE or incense smoke extract (ISE). After 24 h, the barrier function was assessed by measurement of transepithelial electrical resistance (TEER). The quantitative PCR was performed for tight junction (TJ) proteins, including claudin-1, -3, -4, -7 and -15, occludin, zonula occludens-1 (ZO-1), E-cadherin and junctional adhesion molecule -A (JAM-A). RESULTS: TEER was decreased by CSE and ISE in concentration-dependent manner, suggesting the impairment of barrier function. The expressions of claudin-1, -3, -4 and -7, occludin, E-cadherin and JAM-A were decreased by CSE. The CSE-induced decrease in TEER was significantly attenuated by pretreatment with corticosteroid alone but not with LABA alone. The attenuation by corticosteroid was not augmented by addition of LABA. The decreased gene expressions of TJ proteins were unaffected by corticosteroid, LABA, or their combination. The ISE-induced barrier dysfunction was not attenuated by corticosteroid alone, LABA alone, or their combination. CONCLUSION: LABA in addition to corticosteroid had no synergistic effect on CSE- or ISE-induced epithelial barrier dysfunction. Exposure to incense smoke may induce corticosteroid-resistant impairment of airway barrier system.