Notch signal suppresses Toll-like receptor-triggered inflammatory responses in macrophages by inhibiting extracellular signal-regulated kinase 1/2-mediated nuclear factor κB activation.

ABSTRACT: Multiple signaling pathways are involved in the tight regulation of Toll-like receptor (TLR) signaling, which is important for the tailoring of inflammatory response to pathogens in macrophages. It is widely accepted that TLR signaling can activate Notch pathway; however, whether full activation of Notch signaling can feedback modulate TLR signaling pathway so as to control inflammation response remains unclear. Here, we demonstrated that stimulation with TLR ligands up-regulated Notch1 and Notch2 expression in macrophages. The expression of Notch target genes including Hes1 and Hes5 was also induced in macrophages by LPS, suggesting that TLR4 signaling enhances the activation of Notch pathway. Importantly, overexpression of constituted active form of Notch1 (NICD1) and Notch2 (NICD2) supp

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC3307302 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature