Role of interleukin-6 in elastase-induced lung inflammatory changes in mice

Sadatomo Tasaka, Ken Ichiro Inoue, Keisuke Miyamoto, Yasushi Nakano, Hirofumi Kamata, Hiromi Shinoda, Naoki Hasegawa, Taku Miyasho, Masahiko Satoh, Hirohisa Takano, Akitoshi Ishizaka

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18 Citations (Scopus)

Abstract

Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in the development of pulmonary emphysema remains unclear. Wild-type (WT) and IL-6deficient mice received either phosphate-buffered saline (PBS) or porcine pancreatic elastase (PPE) intratracheally. The development of emphysema was determined by measuring the mean linear intercept (Lm). The lung specimens were also subjected to immunohistochemistry for single-stranded DNA to detect apoptotic cells. Lung mechanics and airway responsiveness to inhaled methacholine were analyzed. Bronchoalveolar lavage (BAL) fluid was subjected to evaluation of inflammatory cell accumulation and cytokine measurement. PPE treatment caused significant increases in Lm and lung compliance, which was attenuated by IL-6 deficiency. The increases in apoptotic cells in the lung were attenuated in IL-6 null mice. Airway responsiveness was not affected by PPE challenge or IL-6 deficiency. Intratracheal PPE increased the cell counts in BAL fluid throughout the observation, which was suppressed in IL-6 null mice. In BAL fluid, PPE-induced increases in the levels of macrophage inflammatory protein (MIP)-1α and eotaxin were mitigated by IL-6 deficiency. PPE-induced up-regulation of matrix metalloproteinase (MMP)-12 in the lung was attenuated by IL-6 deficiency. These results indicate that IL-6 may play an important role in the development of elastase-induced lung inflammatory changes.

Original languageEnglish
Pages (from-to)362-372
Number of pages11
JournalExperimental Lung Research
Volume36
Issue number6
DOIs
Publication statusPublished - 2010 Jul

Keywords

  • IL-6
  • MMP-12
  • apoptosis
  • elastase
  • emphysema

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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  • Cite this

    Tasaka, S., Inoue, K. I., Miyamoto, K., Nakano, Y., Kamata, H., Shinoda, H., Hasegawa, N., Miyasho, T., Satoh, M., Takano, H., & Ishizaka, A. (2010). Role of interleukin-6 in elastase-induced lung inflammatory changes in mice. Experimental Lung Research, 36(6), 362-372. https://doi.org/10.3109/01902141003678590