The Role of Transglutaminase-2 in Fibroproliferation after Lipopolysaccharide-induced Acute Lung Injury

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 μL of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/50 μL 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)-κB were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-β1 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-α and IL-1β concentrations and NF-κB 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-β1 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.