HES1 and Hepatitis: 18 Induction of the Notch intracellular domain (NICD) suppresses proinflammatory cytokine expression while enhancing anti-inflammatory mediator expression in TLR-stimulated macrophages.19 Moreover, Notch1 and its target gene Hes1 can inhibit the inflammatory response via an inhibitory feedback loop and transcriptional regulation.20,21 Disruption of myeloid Notch1 activity activates RhoA/ROCK signaling and exacerbates liver inflammation.22 These results suggest that Notch signaling modulates the inflammatory response through multiple mechanisms.