Blood · 2010 · 53 citations · 29 references
Life SciencesImmunologyMolecular BiologyCell SignalingInnate ImmunitySignal TransductionInflammatory Cell ResponsesInflammatory Response RegulationInflammatory SignalingInnate Immune Signaling PathwaysMacrophage BiologyToll-like ReceptorsGlucocorticoid-mediated Immune SignalingMacrophage Toll-like Receptor SignalingToll-like Receptor SignalingToll-like Receptor Signaling CascadesToll-like Receptor Signaling PathwaysToll-like Receptor-mediated Cytokine InductionToll-like Receptors In Inflammation
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.
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Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Björn E. Clausen, Christoph Burkhardt, Walter Reith et al. · Transgenic Research · 1999 · 2.2K citations
Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
Kasper Hoebe, Xin Du, Philippe Georgel et al. · Nature · 2003 · 1.2K citations