Decreased expression of antioxidant enzymes and increased expression of chemokines in COPD lung

Masafumi Tomaki, Hisatoshi Sugiura, Akira Koarai, Yuichi Komaki, Takefumi Akita, Tatsumi Matsumoto, Atsushi Nakanishi, Hiromasa Ogawa, Toshio Hattori, Masakazu Ichinose

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

The involvement of inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD) has been investigated using samples from relatively central airways such as airway biopsies, but there have been fewer studies in the peripheral lung, which is thought to be the main site of the disease process. To determine the molecules that relate to the mechanisms underlying the pathogenesis of COPD, we evaluated the mRNA expression of inflammatory cytokines, chemokines, oxidant enzymes, antioxidant enzymes, proteinases and antiproteinases in peripheral lung tissues from 33 COPD and non-COPD subjects who were undergoing lung resection for lung cancer using an RT-PCR technique. Among the 42 studied candidate genes, the expressions of mRNA for catalase, glutathion S-transferase P1 (GSTP1), glutathion S-transferase M1 (GSTM1), microsomal epoxide hydrolase (mEPHX) and tissue inhibitor of metalloproteinase 2 (TIMP2) were significantly decreased in COPD lung tissues compared with those in non-COPD tissues, and most of these decreases were significantly correlated with the degree of airflow limitation. On the other hand, the expressions of mRNA for interleukin 1β (IL-1β), interleukin 8 (IL-8), growth-related oncogene-α (Gro-α) and monocyte chemotactic protein-1 (MCP-1) were significantly increased in COPD lungs. Most of these changes were also associated with cigarette smoking. These data suggest that an impairment of protective mechanisms against oxidants and xenobiotics, in addition to the upregulation of CXC- and CC-chemokines, may be associated with cigarette smoking and involved in the inflammatory process of COPD.

Original languageEnglish
Pages (from-to)596-605
Number of pages10
JournalPulmonary Pharmacology and Therapeutics
Volume20
Issue number5
DOIs
Publication statusPublished - 2007 Oct

Keywords

  • Catalase
  • Glutathion S-transferase M1
  • Glutathion S-transferase P1
  • Microsomal epoxide hydrolase
  • RT-PCR
  • Tissue inhibitor of metalloproteinase 2
  • mRNA

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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