Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study
Open Access
- 18 December 2009
- journal article
- Published by Springer Science and Business Media LLC in Respiratory Research
- Vol. 10 (1), 126
- https://doi.org/10.1186/1465-9921-10-126
Abstract
Background Toll-like receptor 4 (TLR4) is essential in lipopolysaccharide (LPS)-induced fibroblast activation and collagen secretion in vitro. However, its effects on the process of lung fibroblast activation and fibrosis initiation during LPS induced acute lung injury (ALI) remain unknown. The goal of the present study was to determine the effect of inhibiting TLR4 on LPS-induced ALI and fibrosis in vivo. Methods The ALI model was established by intraperitoneal injection of LPS in mice. TLR4-small hairpin RNA (shRNA) lentivirus was injected intravenously into the mice to inhibit TLR4 expression. mRNA and protein levels were detected by real-time PCR and Western-blot analysis, respectively. The contents of the C-terminal propeptide of type I procollagen (PICP) in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the degree of fibrosis was detected by van Gieson collagen staining, the hydroxyproline assay, and alpha smooth muscle actin (α-SMA) immunohistochemical staining. Results Overexpression of TLR4, type I procollagen, alpha-SMA, and p-AKT in murine pulmonary tissue after intraperitoneal injection of LPS at 72 hours and 28 days were detected. Moreover, the degree of fibrosis was shown to increase by ELISA analysis of PICP in BALF, van Gieson collagen staining, the hydroxyproline assay, and α-SMA immunohistochemical staining. All of these changes were alleviated by intravenous infection with TLR4-shRNA lentivirus. Conclusions Inhibiting TLR4 signaling could ameliorate fibrosis at the early stage of ALI induced by LPS.Keywords
This publication has 31 references indexed in Scilit:
- Toll-like receptor 4 mediates lipopolysaccharide-induced collagen secretion by phosphoinositide3-kinase-akt pathway in fibroblasts during acute lung injuryJournal of Receptors and Signal Transduction, 2009
- TLR4 is Essential in Acute Lung Injury Induced by Unresuscitated Hemorrhagic ShockJournal Of Trauma-Injury Infection and Critical Care, 2009
- CD19 Regulates Skin and Lung Fibrosis via Toll-Like Receptor Signaling in a Model of Bleomycin-Induced SclerodermaThe American Journal of Pathology, 2008
- Semaphorin 7A plays a critical role in TGF-β1–induced pulmonary fibrosisThe Journal of Experimental Medicine, 2007
- Role of Toll-like receptor 4 for the pathogenesis of acute lung injury in Gram-negative sepsisEuropean Journal of Anaesthesiology, 2006
- Gene expression of Toll-like receptor-2, Toll-like receptor-4, and MD2 is differentially regulated in rabbits with Escherichia coli pneumoniaGene, 2005
- Endothelin-1 Promotes Myofibroblast Induction through the ETA Receptor via a rac/Phosphoinositide 3-Kinase/Akt-dependent Pathway and Is Essential for the Enhanced Contractile Phenotype of Fibrotic FibroblastsMolecular Biology of the Cell, 2004
- Role ofToll-Like Receptor 4 in Gram-Positive and Gram-Negative Pneumonia inMiceInfection and Immunity, 2004
- A Novel Method to Compensate for Different Amplification Efficiencies between Patient DNA Samples in Quantitative Real-Time PCRThe Journal of Molecular Diagnostics, 2001
- Gelatinase B Is Required for Alveolar Bronchiolization after Intratracheal BleomycinThe American Journal of Pathology, 2000