TAK1 targeting by glucocorticoids determines JNK and IkappaB regulation in Toll-like receptor-stimulated macrophages.
Blood
; 115(10): 1921-31, 2010 Mar 11.
Article
in En
| MEDLINE
| ID: mdl-20065289
ABSTRACT
Glucocorticoids potently attenuate the production of inflammatory mediators by macrophages, a primary effector of innate immunity. Activation of different macrophage Toll-like receptors (TLRs) by their respective ligands presents a powerful system by which to evaluate stimulus-dependent glucocorticoid effects in the same cell type. Here, we test the hypothesis that glucocorticoids, acting through the glucocorticoid receptor, modulate macrophage activation preferentially depending upon the TLR-selective ligand and TLR adapters. We established that 2 adapters, Trif, MyD88, or both, determine the ability of glucocorticoids to suppress inhibitor of kappaB (IkappaB) degradation or Janus kinase (JNK) activation. Moreover, the sensitivity of transforming growth factor beta-activated kinase 1 (TAK1) activation to glucocorticoids determines these effects. These findings identify TAK1 as a novel target for glucocorticoids that integrates their anti-inflammatory action in innate immunity signaling pathways.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polydeoxyribonucleotides
/
MAP Kinase Kinase Kinases
/
I-kappa B Proteins
/
JNK Mitogen-Activated Protein Kinases
/
Toll-Like Receptors
/
Glucocorticoids
/
Macrophage Activation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Blood
Year:
2010
Document type:
Article
Affiliation country:
United States