Neutralization of IL-18 by IL-18 binding protein ameliorates bleomycin-induced pulmonary fibrosis via inhibition of epithelial-mesenchymal transition.

摘要: Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal parenchymal lung disease with limited effective therapies. Interleukin (IL)-18 belongs to rather large IL-1 gene family and proinflammatory cytokine, which acts in both acquired innate immunity. We have previously reported that IL-18 play an important role lipopolysaccharide-induced acute injury mice. Persistent inflammation often drives fibrotic progression the bleomycin (BLM) model. However, of (PF) still unknown. binding protein (IL-18BP) able neutralize biological activity has protective effect against renal fibrosis. The aim this study was investigate effects IL-18BP on BLM-induced PF. In present study, we found upregulated lungs BLM-injured Neutralization by improved survival rate ameliorated PF mice, associated attenuated pathological changes, reduced collagen deposition, decreased content transforming growth factor-β1 (TGF-β1). further demonstrated treatment suppressed epithelial mesenchymal transition (EMT), characterized α-smooth muscle actin (α-SMA) increased E-cadherin (E-cad) in vivo. addition, provided in vitro evidence demonstrating promoted EMT through upregulation Snail-1 A549 cells. conclusion, our findings raise possibility increase involved development modulating Snail-1-dependent manner. may be worthwhile candidate option for therapy.