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

Research output: Contribution to journalArticle

16 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

Fingerprint

Pancreatic Elastase
Interleukin-6
Swine
Lung
Bronchoalveolar Lavage Fluid
Fluids
Matrix Metalloproteinase 12
Lung Compliance
Macrophage Inflammatory Proteins
Cells
Pulmonary Emphysema
Methacholine Chloride
Single-Stranded DNA
Emphysema
Mechanics
Up-Regulation
Cell Count
Immunohistochemistry
Phosphates
Observation

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Medicine(all)

Cite this

Tasaka, S., Inoue, K. I., Miyamoto, K., Nakano, Y., Kamata, H., Shinoda, 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

Role of interleukin-6 in elastase-induced lung inflammatory changes in mice. / Tasaka, Sadatomo; Inoue, Ken Ichiro; Miyamoto, Keisuke; Nakano, Yasushi; Kamata, Hirofumi; Shinoda, Hiromi; Hasegawa, Naoki; Miyasho, Taku; Satoh, Masahiko; Takano, Hirohisa; Ishizaka, Akitoshi.

In: Experimental Lung Research, Vol. 36, No. 6, 2010, p. 362-372.

Research output: Contribution to journalArticle

Tasaka, S, Inoue, KI, 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, vol. 36, no. 6, pp. 362-372. https://doi.org/10.3109/01902141003678590
Tasaka, Sadatomo ; Inoue, Ken Ichiro ; Miyamoto, Keisuke ; Nakano, Yasushi ; Kamata, Hirofumi ; Shinoda, Hiromi ; Hasegawa, Naoki ; Miyasho, Taku ; Satoh, Masahiko ; Takano, Hirohisa ; Ishizaka, Akitoshi. / Role of interleukin-6 in elastase-induced lung inflammatory changes in mice. In: Experimental Lung Research. 2010 ; Vol. 36, No. 6. pp. 362-372.
@article{4f104b82ca234d1e8facddd60bbe7a23,
title = "Role of interleukin-6 in elastase-induced lung inflammatory changes in mice",
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.",
keywords = "apoptosis, elastase, emphysema, IL-6, MMP-12",
author = "Sadatomo Tasaka and Inoue, {Ken Ichiro} and Keisuke Miyamoto and Yasushi Nakano and Hirofumi Kamata and Hiromi Shinoda and Naoki Hasegawa and Taku Miyasho and Masahiko Satoh and Hirohisa Takano and Akitoshi Ishizaka",
year = "2010",
doi = "10.3109/01902141003678590",
language = "English",
volume = "36",
pages = "362--372",
journal = "Experimental Lung Research",
issn = "0190-2148",
publisher = "Informa Healthcare",
number = "6",

}

TY - JOUR

T1 - Role of interleukin-6 in elastase-induced lung inflammatory changes in mice

AU - Tasaka, Sadatomo

AU - Inoue, Ken Ichiro

AU - Miyamoto, Keisuke

AU - Nakano, Yasushi

AU - Kamata, Hirofumi

AU - Shinoda, Hiromi

AU - Hasegawa, Naoki

AU - Miyasho, Taku

AU - Satoh, Masahiko

AU - Takano, Hirohisa

AU - Ishizaka, Akitoshi

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - apoptosis

KW - elastase

KW - emphysema

KW - IL-6

KW - MMP-12

UR - http://www.scopus.com/inward/record.url?scp=77954960884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954960884&partnerID=8YFLogxK

U2 - 10.3109/01902141003678590

DO - 10.3109/01902141003678590

M3 - Article

VL - 36

SP - 362

EP - 372

JO - Experimental Lung Research

JF - Experimental Lung Research

SN - 0190-2148

IS - 6

ER -