3069 – Chronic Inflammation Decreases HSC Fitness via Hyperactivation of the Druggable Il-6/Stat3 Signaling Pathway

SHP-1 interacts with NFκB1 to inhibit its phosphorylation and nuclear translocation to suppress excessive bacterial inflammation

“…An effective host defense against fulminant pathogen infection depends on the orchestrated balance of robust inflammatory/immune response and the timely control of these responses to avoid tissue damage and even death. Dysregulated inflammatory response can lead to the overactivation of multiple signaling pathways, including but not limited to NFκB (12)(13)(14)(15), toll like receptor 5-myeloid differentiation primary response 88 (TLR5-MYD88) (16,17), and STAT3 (18)(19)(20) signaling, resulting in the occurrence of cytokine storms with the overexpression of interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon gamma (IFN-γ), and tumor necrosis factor-α (TNF-α), threatening the host's life (21). These emphasize the importance of negative regulation of the overactivated inflammatory/immune response, highlighting the necessity to elaborate the role and molecular mechanisms of SHP-1 in these signaling pathways.…”