Toll-like receptor 4 promotes fibrosis in bleomycin-induced lung injury in mice

作者：Li, X. X.; Jiang, D. Y.; Huang, X. X.; Guo, S. L.; Yuan, W.; Dai, H. P.^*

来源：Genetics and Molecular Research, 2015, 14(4): 17391-17398.

DOI：10.4238/2015.December.21.8

• Bleomycin
• Idiopathic pulmonary fibrosis
• Lung fibrosis
• Toll-like receptor

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.

• 出版日期2015
• 单位首都医科大学