Decreased expression of antioxidant enzymes and increased expression of chemokines in COPD lung.
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 1beta (IL-1beta), interleukin 8 (IL-8), growth-related oncogene-alpha (Gro-alpha) 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.
Tomaki
Masafumi
M
Division of Respiratory and Infectious Diseases, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Sugiura
Hisatoshi
H
Koarai
Akira
A
Komaki
Yuichi
Y
Akita
Takefumi
T
Matsumoto
Tatsumi
T
Nakanishi
Atsushi
A
Ogawa
Hiromasa
H
Hattori
Toshio
T
Ichinose
Masakazu
M
D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000378:metabolism; D011013:Pneumonectomy; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects; D015854:Up-Regulation
D000975:Antioxidants; D018925:Chemokines; D004798:Enzymes; D016877:Oxidants; D012333:RNA, Messenger