Abstract
Triggering receptor expressed on myeloid cells 1 (TREM-1) increases the expression of TGF-β family genes, which are known as profibrogenic cytokines in the pathogenesis of pulmonary fibrosis. In this study, we determined whether TGF-β1 regulated the expression of TREM-1 in a mouse model of pulmonary fibrosis. The expression of TGF-β1 and TREM-1 was increased on day 7, 14, and 21 after single intratracheal injection of bleomycin (BLM). And there was positive correlation between the expression of TGF-β1 and TREM-1. TGF-β1 increased expression of TREM-1 mRNA and protein in a time- and dose-dependent manner in mouse macrophages. The expression of the activator protein 1 (AP-1) was increased in lung tissues from mouse after BLM injection and in mouse macrophages after TGF-β1 treatment, respectively. TGF-β1 significantly increased the relative activity of luciferase in the cells transfected with plasmid contenting wild type-promoter of TREM-1. But TGF-β1 had no effect on the activity of luciferase in the cells transfected with a mutant-TREM1 plasmid carrying mutations in the AP-1 promoter binding site. In conclusion, we found the expression of TREM-1 was increased in lung tissues from mice with pulmonary fibrosis. TGF-β1 increased the expression of TREM-1 in mouse macrophages partly via the transcription factor AP-1.
Highlights
Differentiation of fibroblasts, epithelial-mesenchymal transition (EMT), and transformation of lung fibroblasts to myofibroblasts, which eventually lead to serious pulmonary fibrosis in vivo and in vitro[17,18,19]
The deposition of collagen in lung tissues was detected by Masson staining, and we found the quantity of collagen increased dramatically and extensive pulmonary fibrosis was formed on days 7, 14 and 21 in mice from the BLM-treated group in comparison with the control group (Fig. S1g–l)
The results showed that Triggering receptor expressed on myeloid cells 1 (TREM-1) protein level was not altered following 1, 2, 5, and 10 h incubation with 10 ng/ml transforming growth factor (TGF)-β 1 (p > 0.05), but there was a distinct increase at 20 h and 40 h, with the highest expression level at 20 h after TGF-β 1 stimulation in primary alveolar macrophages (p < 0.05) (Fig. 3a,b)
Summary
Differentiation of fibroblasts, epithelial-mesenchymal transition (EMT), and transformation of lung fibroblasts to myofibroblasts, which eventually lead to serious pulmonary fibrosis in vivo and in vitro[17,18,19]. TGF-β 1 is a central node in the pulmonary fibrosis pathogenesis pathway, while TREM-1 activation dramatically increases the expression of TGF-β family genes. It remains unknown whether the increase of TGF-β 1 could affect the expression of TREM-1. This study was designed to determine the effect of TGF-β 1 on the expression of TREM-1 in lungs and to explore the transcriptional mechanism at both the organismal and cellular levels, which will provide novel insights into the regulatory mechanisms in the pathogenesis of pulmonary fibrosis, and the potential therapeutic targets for the treatment of pulmonary fibrosis
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