Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK.
J Cell Physiol
; 229(7): 845-55, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24265116
ABSTRACT
The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-κB- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H(2)O(2) generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H(2)O(2) generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fibrose
/
Aspirina
/
Interleucina-18
/
Proteínas Ligadas por GPI
/
Miocárdio
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2014
Tipo de documento:
Article