Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 1075-1080

Inhalant Corticosteroids Inhibit Hyperosmolarity-induced, and Cooling and Rewarming-induced Interleukin-8 and RANTES Production by Human Bronchial Epithelial Cells

SHU HASHIMOTO, YASUHIRO GON, KEN MATSUMOTO, IKUKO TAKESHITA, SHUICHIRO MARUOKA, and TAKASHI HORIE

First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH₂-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming-induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming-induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid-mediated inhibition of hyperosmolarity-induced, and cooling and rewarming- induced cytokine production remains to be clarified.

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