Suppression of IL-8 production from airway cells by tiotropium bromide in vitro.

Isao Suzaki, Kazuhito Asano, Yusuke Shikama, Taisuke Hamasaki, Ayako Kanei, Harumi Suzaki

Department of Otorhinolaryngology, School of Medicine, Showa University, Tokyo, Japan.

International journal of chronic obstructive pulmonary disease 2011

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COPD is characterized by persistent and progressive airway inflammation. Although neutrophilic airway inflammation is generally accepted to be a major factor in the pathogenesis of COPD, the influence of the agents used for the treatment of COPD on neutrophil functions such as chemotaxis is not fully understood. The present study aimed to examine the influence of tiotropium bromide on the production of interleukin (IL)-8 from human airway epithelial cells and lung fibroblasts (LFs) after lipopolysaccharide (LPS) stimulation in vitro. BEAS-2B cells, human bronchial epithelial cell line, and LFs, at a concentration of 5 × 10(5) cells/mL, were stimulated with LPS in the presence of various concentrations of tiotropium bromide. IL-8 in culture supernatants was examined by enzyme-linked immunosorbent assay (ELISA). IL-8 messenger ribonucleic acid (mRNA) expression was examined by real-time polymerase chain reaction. The influence of tiotropium bromide on LPS-induced signaling pathways was also analyzed by examining nuclear factor-kappa (NF-κ)B activation and signaling protein phosphorylation by ELISA. Tiotropium bromide at > 15 pg/mL inhibited IL-8 production from both BEAS-2B cells and LFs after LPS stimulation. Tiotropium bromide also suppressed IL-8 mRNA expression through the inhibition of NF-κB activation and signaling protein, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase, phosphorylation. The present results strongly suggest that tiotropium bromide exerts the inhibitory effect on neutrophilic inflammation through the suppression of IL-8 production from epithelial cells and LFs by interfering with LPS-mediated signaling pathways and thus may contribute to lower cellular inflammation in COPD, which is responsible for favorable modification of the disease.

Citation

Isao Suzaki, Kazuhito Asano, Yusuke Shikama, Taisuke Hamasaki, Ayako Kanei, Harumi Suzaki. Suppression of IL-8 production from airway cells by tiotropium bromide in vitro. International journal of chronic obstructive pulmonary disease. 2011;6:439-48