Toll like receptor 2 mediates bleomycin-induced acute lung injury, inflammation and fibrosis in mice
- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 8
- DOI:
- No doi available
- Key Word:
- TLR2;博莱霉素;树突状细胞;肺部炎症;急性肺损伤;纤维化;TLR2;bleomycin;dendritic cell;pulmonary inflammation;acute lung injury;fibrosis
Abstract： Anti cancer drug bleomycin (BLM) can cause acute lung injury (ALl) which often results in pulmonary fibrosis due to a failure of resolving acute inflammatory response. The aim of this study is to investigate whether toll-like receptor (TLR) 2 mediates BLM induced ALI. inflammation and fibrosis.BLM-induced dendritic cells (DCs) maturation was analyzed by flow cytometry and cytokine secretion was detected by the ELISA method. The expression and activity of p38 and ERK MAPK were determined with Western blotting. The roles of TLR2 in ALI, inflammation and fibrosis were investigated in C57BL/6 mice administered intratracheally with BLM.The resuts demonstrated that BLM administered mice had higher expression of TLR2 (P < 0001) and its signaling molecules. Blocking TLR2 significantly inhibited the maturation of DCs and reversed BLM-stimulated secretion of cytokines in DCs, such as IL-6 (P<0.001), IL-17(P<0.05) and IL-23 (P<0.05). TLR2 inhibition attenuated BLM induced increase of inflammatory cells in bronchoalveolar lavage fuid (BALF), and reversed the immunosuppressive microenvironment by enhancing TH1 response (P<0 05) and inhibiting TH2 (P<0 001), Trcg (P<0 01) and TH17 (P<001) responses Importantly,blocking TLR2 in vivo significantly protected BLM-administcrcd mice from pulmonary injury, inflammation and fibrosis and subsequenfiy increased BLM-induced animal survival (from 50% to 92%) Therefore, TLR2 is a novel potential target for ALl and pulmonary fibrosis.
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