Abstract
Liver sinusoidal endothelial cells (ECs) of the nonembolized hepatic lobe are stretched continuously followed by the increase in blood flow after portal vein embolization. Previously, we showed that ECs secret IL-6, a trigger of liver regeneration, via NF-κB pathway when they were subjected to continuous stretch on an elastic silicone chamber. In this study, we examined the mechanism of NF-κB activation in response to uni-axial continuous stretch in ECs. 1) Continuous stretch-induced NF-κB activation was inhibited by the application ofα5β1 integrin inhibitory peptide: GRGDNP, phospholipase C inhibitor: U73122, PKC inhibitor: H7 or the depletion of intra- and extracellular Ca2+ pools by both EGTA and thapsigargin (TG), but not inhibited by the application of a blocker for stretch-activeted channels: Gadolinium (Gd3+), the depletion of extracellular Ca2+ by EGTA or the depletion of intracellular Ca2+ stores by TG. 2) PKC kinase activity was inhibited by the application of GRGDNP or U73122 and the deplation of intra- and extracellular Ca2+ pools by both EGTA and TG. 3) Iincrease in intracellular Ca2+ concentration in response to continuous stretch was observed in the presence of EGTA or TG, but not observed in the presence of both EGTA and TG. These results indicate that NF-κB activation following IL-6 secration in response to continuous stretch is dependent on outside-in signaling at integrins followed by Ca2+-dependent PLC/PKC signaling pathway. [Jpn J Physiol 54 Suppl:S84 (2004)]
