Effects of fty-720 on pulmonary fibrosis in mice via tgf-pl/p38 mapk/nf-kb signaling pathway / 中国药理学通报

ABSTRACT

Aim To investigate the effect of FTY-720 on bleomycin-induced pulmonary fibrosis in mice and its mechanism. Methods Forty specific pathogen-free healthy male BALB/c mice were randomly divided into control group, BLM group, NS + FTY-720 control group, and BLM + FTY-720 group, with 5 mice in each group, and the mice were sacrificed on 7th day and 14th day for a total of 8 groups. Lung tissue inflammation and pulmonary fibrosis were observed by HE staining and Masson staining; Bronchoalveolar lavage fluid (BALF) cells were counted by Swiss-Giemsa staining; BALF protein content was determined by BCA assay; the expression levels of inflammatory cytokines IL-IP and TNF-a in BALF supernatant were measured by ELISA; the expression levels of COL1A1 in lung tissues were detected by immunohistochemis-try; and the expression levels of TGF-|31, p-p38 MAPK and NF-kB were detected by Western blot. Results FTY-720 significantly reduced BLM-induced increase of extracellular collagen deposition in lung tissues of mice, reduced IL-1(3 and TNF-a content in BALF of mice, and reduced the protein content and cell number in BALF of mice; FTY-720 inhibited TGF-(31 activity and p38 MAPK phosphorylation, and then inhibited the expression and activation of NF-kB. Conclusions FTY-720 inhibits bleomycin-induced lung fibrosis in mice by inhibiting the TGF-(31/p38 MAPK/NF-kB signaling pathway.