Gremlin-1 C-Terminus Regulates Function of Macrophage Migration Inhibitory Factor (MIF).
Cell Physiol Biochem
; 38(2): 801-8, 2016.
Article
em En
| MEDLINE
| ID: mdl-26872252
ABSTRACT
BACKGROUND/AIMS:
The counterbalance of macrophage migration inhibitory factor (MIF) and Gremlin-1 is a useful tool to predict the acuity of coronary artery disease (CAD) and plaque stability. Gremlin1 is an endogenous antagonist of MIF and therefore influences plaque vulnerability. This study was designed to elucidate the mechanistic basis determining the biophysical binding of Gremlin-1 to MIF.METHODS:
An in silico model suggested that several charged C-terminal amino acids are crucial in mediating Gremlin-1/MIF-binding. We produced several single amino acid exchange mutants of Gremlin-1 by site-directed mutagenesis. These Gremlin-1 mutants were tested for their ability to reduce MIF effects on monocytes.RESULTS:
We observed that the critical element of the Gremlin-1 molecule for regulating MIF-induced chemotactic activity lies at the C-terminal region. A single amino acid exchange of an arginine to an alanine residue is sufficient to abolish the antagonistic effect of Gremlin-1 on MIF. Therefore, the Gremlin-1 mutant R172A failed to reduce MIF-induced monocyte differentiation into macrophages.CONCLUSION:
Gremlin-1 C-terminus is essential for antagonizing MIF effects. Our results could offer a novel strategy utilizing Gremlin-1 to target pro-inflammatory effects of MIF in various diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores Inibidores da Migração de Macrófagos
/
Oxirredutases Intramoleculares
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha