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: Atsuyasu Sato, Yuma Hoshino, Tomijiro Hara, Shigeo Muro, Hajime Nakamura, Michiaki Mishima, Junji Yodoi
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 325 Issue 2 Pg. 380-8 (May 2008) ISSN: 1521-0103 [Electronic] United States
• PMID: 18256171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Chemokine CXCL2
• Cxcl2 protein, mouse
• RNA, Messenger
• Recombinant Proteins
• Smoke
• Tumor Necrosis Factor-alpha
• Thioredoxins
• Matrix Metalloproteinase 12

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Apoptosis (drug effects)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Chemokine CXCL2 (genetics)
• Humans
• Macrophages (drug effects, immunology)
• Male
• Matrix Metalloproteinase 12 (genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neutrophils (drug effects, immunology)
• Oxidative Stress (drug effects)
• Pneumonia (chemically induced, drug therapy, immunology, pathology)
• Pulmonary Emphysema (chemically induced, drug therapy, immunology, pathology)
• RNA, Messenger (metabolism)
• Recombinant Proteins (genetics, therapeutic use)
• Smoke (adverse effects)
• Thioredoxins (genetics, immunology, therapeutic use)
• Tobacco (adverse effects)
• Tumor Necrosis Factor-alpha (blood, genetics)