| The Role of Transglutaminase-2 in Fibroproliferation after Lipopolysaccharide-induced Acute Lung Injury. |
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Je Hyeong Kim |
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Division of Pulmonary, Sleep and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea. chepraxis@korea.ac.kr |
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| Abstract |
BACKGROUND
Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. METHODS: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which 50 microL of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/50 microL of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor (NF)-kappaB were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-beta1 were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory's phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. RESULTS: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-alpha and IL-1beta concentrations and NF-kappaB activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-beta1 concentration, and Mallory's PTAH stain than the LPS group, but the differences were not significant (p>0.05). CONCLUSION: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters. |
| Key Words:
Acute Lung Injury, Lipopolysaccharides, Inflammation, Fibrosis |
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