Persistent activation of nuclear factor-?B in cultured rat hepatic stellate cells involves the induction of potentially novel rel-like factors and prolonged changes in the expression of I?B family proteins

Proteasome inhibition induces hepatic stellate cell apoptosis

“…Nuclear fluorescence characteristics of translocated RelA/p65 protein were observed under basal condition consistent with the constitutive activated state of these cells. 9 In contrast, RelA/p65 immunofluorescence was cytoplasmic and excluded from the nucleus in bortezomib-treated cells ( Fig. 2A).…”

“…7,8 HSC activation is associated with activation of nuclear factor kappa B (NF-B), a potent prosurvival transcription factor. 9 Inhibition of NF-B activation has been associated with apoptosis-induction in many cancer cells. 10 Although it has been reported that NF-B inhibition does not result in HSC apoptosis, 7 several studies have indicated that NF-B inhibition is a potent mechanism to induce HSC apoptosis.…”

Epigenetic Modifications in Hepatic Stellate Cells Contribute to Liver Fibrosis

“…However, situation changes when liver injury occurs. Adipogenic genes (such as PPAR-γ, enhancer binding protein and inhibitor of nuclear factor-κB protein-α) are down-regulated or silenced in response to liver injury (Elsharkawy et al 1999;Miyahara et al 2000;Oakley et al 2003;She et al 2005), and HSC differentiation is taken over by myogenic genes (such as collagens I and III, TIMP-1, α-SMA, interleukin-6) (Bataller and Brenner 2005;Friedman 2008). …”

Nuclear factor-κB and the hepatic inflammation-fibrosis-cancer axis

“…11 NF-B activation is associated with the transdifferentiation of hepatic stellate cells (HSCs) into scar-forming hepatic myofibroblasts, an event that is considered pivotal in the fibrogenic response. 12 NF-B is activated in HSCs in response to carbon tetrachloride injury and stimulates expression of proinflammatory molecules (IL-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1) and antiapoptotic factors (growth arrest and DNA damage-inducible gene 45␤) required for HSC function and survival during the fibrogenic response. 13 The induction of hepatocyte NF-B during liver injury has been reported by many laboratories in response to alcohol, endotoxin, TNF-␣, and cholestasis (bile duct ligation).…”