Inflammatory pathways in hepatocytes

Inflammatory pathways in hepatocytes represent a complex network of intracellular signaling cascades, including the NF-κB, JAK/STAT, and JNK/MAPK systems, that coordinate the liver's response to metabolic, toxic, and infectious insults [1, 4]. These pathways are typically triggered by the binding of pro-inflammatory cytokines like TNF-α and IL-6 to their respective receptors or by the activation of pattern recognition receptors such as Toll-like receptors (TLRs) and the STING pathway in response to danger-associated molecular patterns (DAMPs) [2, 5, 8]. While acute activation is essential for host defense, chronic inflammatory signaling in hepatocytes is a primary driver of non-alcoholic steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma (HCC) [4, 6, 10]. Persistent inflammation promotes hepatocyte apoptosis, insulin resistance, and the activation of hepatic stellate cells, which drive the progression of chronic liver disease [4, 9]. Pharmacological targeting of specific nodes within these pathways, such as the use of NLRP3 inhibitors or STING antagonists, is currently being explored to mitigate liver damage and prevent disease progression [2, 4]. However, therapeutic intervention is challenging due to the essential role of these pathways in normal liver homeostasis and the potential for systemic side effects like impaired tissue repair or increased susceptibility to infections [1, 5].

Other names

Hepatocyte inflammatory signalingIntrahepatic inflammatory cascadesPro-inflammatory pathways in liver cells

Inhibition of pro-inflammatory signaling nodes such as the NLRP3 inflammasome, STING pathway, or cytokine receptors (e.g., IL-6R, TNFR) to prevent downstream activation of NF-κB and JNK, thereby reducing hepatocyte injury and fibrogenic signaling.