title: Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice.
abstract: Cigarette smoking is associated with the development of inflammatory lung diseases representing major health problems world-wide. We hypothesized that the redox-regulating molecule thioredoxin-1 (TRX), which shows anti-inflammatory, antioxidative, and antiapoptotic effects, could be induced by cigarette smoke (CS) and contribute to protect against CS-induced inflammation and lung destruction. In an acute study, human TRX transgenic mice and C57BL6/J mice were exposed to mainstream CS for 3 days. In the lungs of CS-exposed mice, bronchial epithelial injury and bronchoalveolar lavage neutrophilia were observed. Oxidative stress and apoptosis were enhanced, and the expression of cytokines macrophage inflammatory protein-2 and tumor necrosis factor (TNF)-alpha was increased 15.3- and 2.4-fold, respectively. Compared with C57BL6/J mice, TRX-transgenic mice had significantly less inflammation, oxidative damage, and apoptosis, as well as decreased levels of matrix metalloprotease-12 mRNA and serum TNF-alpha. When recombinant human TRX (40 microg/body/day, 3 days) was injected i.p. into CS-exposed C57BL6/J mice, a significant effect to offer protection against CS-induced lung injury was observed through suppression of neutrophil influx. In the chronic study, TRX-transgenic mice and C57BL6/J mice were exposed to CS for 6 months. This chronic exposure caused pulmonary emphysema in C57BL6/J mice accompanying prominent infiltration of macrophages and neutrophils to lung. These pathological changes were significantly suppressed in TRX-transgenic mice. In conclusion, TRX induction ameliorated CS-induced lung inflammation and emphysema in mice. TRX-1 may therefore play a preventive or therapeutic role in lung inflammatory disorders such as chronic obstructive pulmonary disease.
authors.affiliation: Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 6068507 Japan.
authors.forename: Atsuyasu
authors.initials: A
authors.lastname: Sato
authors.forename: Yuma
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Tomijiro
authors.initials: T
authors.lastname: Hara
authors.forename: Shigeo
authors.initials: S
authors.lastname: Muro
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054426:Chemokine CXCL2 / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D012906:Smoke / Q000009:adverse effects*; D013879:Thioredoxins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014026:Nicotiana / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; D013879:Thioredoxins; D053508:Matrix Metalloproteinase 12