Delta-Like Ligand 4 Modulates Liver Damage by Down-Regulating Chemokine Expression.

Delta-Like Ligand 4 Modulates Liver Damage by Down-Regulating Chemokine Expression. Am J Pathol. 2016 May 9; Authors: Shen Z, Liu Y, Dewidar B, Hu J, Park O, Feng T, Xu C, Yu C, Li Q, Meyer C, Ilkavets I, Müller A, Stump-Guthier C, Munker S, Liebe R, Zimmer V, Lammert F, Mertens PR, Li H, Dijke PT, Augustin HG, Li J, Gao B, Ebert MP, Dooley S, Li Y, Weng HL Abstract Disrupting Notch signaling ameliorates experimental liver fibrosis. However, the role of individual Notch ligands in liver damage is unknown. We investigated the effects of Delta-like ligand 4 (Dll4) in liver disease. DLL4 expression was measured in 31 human liver tissues by immunohistochemistry. Dll4 function was examined in carbon tetrachloride- and bile duct ligation-challenged mouse models in vivo and evaluated in hepatic stellate cells, hepatocytes, and Kupffer cells in vitro. DLL4 was expressed in patients' Kupffer and liver sinusoidal endothelial cells. Recombinant Dll4 protein (rDll4) ameliorated hepatocyte apoptosis, inflammation, and fibrosis in mice after carbon tetrachloride challenge. In vitro, rDll4 significantly decreased lipopolysaccharide-dependent chemokine expression in both Kupffer and hepatic stellate cells. In bile duct ligation mice, rDll4 induced massive hepatic necrosis, resulting in the death of all animals within 1 week. Inflammatory cell infiltration and chemokine ligand 2 (Ccl2) expression were significantly reduced in rDll4-receiving bile...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research