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Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production from stimulated human alveolar epithelial type II cells

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Abstract

Purpose

The alveolar epithelial cell type II (AEC-II) is itself able to amplify lung inflammation by producing inflammatory cytokines and chemokines, leading to the activation and recruitment of phagocytes. Sivelestat, a new neutrophil elastase inhibitor, has been shown to attenuate acute lung injury in animal experiments. In the current study, we assessed the effects of sivelestat on the production of chemokines from cultured A549 cells, a human AEC-II-like cell line.

Methods

A549 cells were stimulated with endotoxin or tumor necrosis factor-α in the presence of sivelestat (1–100 μg·ml−1). Culture supernatant levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay. The expression of IL-8 and MCP-1 mRNAs in stimulated A549 cells in the presence of sivelestat (100 μg·ml−1) was quantified by real-time polymerase chain reaction.

Results

Sivelestat, at 100 μg·ml−1 reduced the accumulation of IL-8 and MCP-1 in the culture medium. The high dose of sivelestat significantly inhibited the expression of IL-8 mRNA in A549 cells. The drug also decreased MCP-1 mRNA expression, although not significantly.

Conclusion

These data suggest that a high dose of sivelestat regulates the production of IL-8 and MCP-1 in AEC-II.

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Authors and Affiliations

  1. Department of Anesthesia and Perioperative Medicine, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Takuyo Misumi, Takanori Tanaka, Katsuya Mikawa, Kahoru Nishina, Osamu Morikawa & Hidefumi Obara

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  1. Takuyo Misumi
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  2. Takanori Tanaka
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  3. Katsuya Mikawa
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  4. Kahoru Nishina
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  5. Osamu Morikawa
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  6. Hidefumi Obara
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Misumi, T., Tanaka, T., Mikawa, K. et al. Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production from stimulated human alveolar epithelial type II cells. J Anesth 20, 159–165 (2006). https://doi.org/10.1007/s00540-006-0391-z

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  • DOI: https://doi.org/10.1007/s00540-006-0391-z

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