title: Toll-like receptor 4 promotes fibrosis in bleomycin-induced lung injury in mice.
abstract: The specific role of Toll-like receptor 4 (TLR4) in bleomycin-induced lung fibrosis of mice, a model of human idiopathic pulmonary fibrosis, has not been characterized. We injected bleomycin intratracheally into TLR4 knockout (TLR4(-/-)) and wild-type (WT) mice. Twenty-one days after injection, mice were sacrificed and their lungs were harvested for pathological, hydroxyproline, mRNA expression, and collagen I analyses. Body weight changes and mortality were observed. Light microscopy showed that lung fibrosis was minimal in TLR4(-/-) compared to that in WT mice on day 21 after bleomycin instillation. The Ashcroft score was significantly lower in TLR4(-/-) than in WT mice (3.667 ± 0.730 vs 4.945 ± 0.880, P < 0.05). Hydroxyproline content was significantly lower in TLR4(-/-) than in WT mice on day 21 after bleomycin injection (0.281 ± 0.022 vs 0.371 ± 0.047, P < 0.05). Compared to WT mice, bleomycin-treated TLR4(-/-) mice expressed significantly lower type I collagen mRNA levels (mesenchymal marker; 11.069 ± 2.627 vs 4.589 ± 1.440, P < 0.05). Collagen I was significantly lower in TLR4(-/-) than in WT mice (0.838 ± 0.352 vs 2.427 ± 0.551, P < 0.05). Bleomycin-treated TLR4(-/-) mice had a significantly lower mortality rate on day 21 than WT mice (33 vs 75%, P < 0.05). Body weight reduction was lower in TLR4(-/-) mice than in WT mice; this difference was not statistically significant (-3.735 ± 5.276 vs -6.698 ± 3.218, P > 0.05). Thus, bleomycin-induced pulmonary fibrosis is TLR4-dependent and TLR4 promoted fibrosis in bleomycin-challenged mice.
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.|Department of Respiratory Medicine, Beijing Shi-Ji Tan Hospital, Capital Medical University, Beijing, China.
authors.forename: X X
authors.initials: XX
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: D Y
authors.initials: DY
authors.lastname: Jiang
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: X X
authors.initials: XX
authors.lastname: Huang
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: S L
authors.initials: SL
authors.lastname: Guo
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
authors.forename: H P
authors.initials: HP
authors.lastname: Dai
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D024042:Collagen Type I / Q000096:biosynthesis; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D006801:Humans; D055370:Lung Injury / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D001761:Bleomycin