The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models.
Biomed Res Int
; 2016: 6306984, 2016.
Article
en En
| MEDLINE
| ID: mdl-27642598
ABSTRACT
Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 1 and 6 1) were treated with four structurally related matriptase inhibitors at 50 µM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21 ± 26.8% in hepatocyte-Kupffer cell, 2 1, and by 42.6 ± 14.3% in hepatocyte-Kupffer cell, 6 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Serina Endopeptidasas
/
Inflamación
/
Hígado
/
Hepatopatías
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Res Int
Año:
2016
Tipo del documento:
Article
País de afiliación:
Hungria