RelB/p50 complexes regulate cytokine-induced YKL-40 expression.

摘要: The secreted protein, YKL-40, has been proposed as a biomarker of variety human diseases characterized by ongoing inflammation, including chronic neurologic pathologies such multiple sclerosis and Alzheimer's disease. However, inflammatory mediators the molecular mechanism responsible for enhanced expression YKL-40 remained elusive. Using several mouse models we now show that correlated with increased both IL-1 IL-6. Furthermore, together IL-6 or family cytokine, oncostatin M, synergistically upregulated in primary astrocytes vitro. robust cytokine-driven required STAT3 NF-κB binding elements promoter. In addition, was constitutively active inhibited dominant-negative IκBα. Surprisingly, independent p65 subunit instead subunits RelB p50. Mechanistically, IL-1-induced RelB/p50 complex formation further promoted M these complexes directly bound to Moreover, found strongly during inflammation vivo We propose cytokines regulate sterile via complexes. These results suggest may specific anti-inflammatory genes nonlymphoid tissues canonical activation