Abstract
DNA fragmentation. Total RNA was isolated and IL-8, CXCL1, CXCL2, CCL2, ICAM, VCAM mRNA expression was determined by real time RT-PCR. NF-kB activation was determined by luciferase assay. Results: Exposure of LX2 cells to palmitate significantly induces IL-8 production and gene expression, as well as TLR4, CXCL1, CXCL2, CCL2, ICAM, VCAM mRNA expression. Palmitate induced IL-8 production can not be blocked by pan-caspase inhibitor. However, palmitate induced MIP-2 (rodent homolog of human IL-8) production was completely abrogated in HSCs from TLR4-mutant (C3H/HeJ) mice, but not from wildtype (C3H/HeOuJ) mice. Palmitate also induces NF-kB activation in a dose-dependent manner. Conclusions: Our data demonstrate that palmitate directly stimulates IL-8 production in HSCs via TLR4 signaling pathway, suggesting that HSCs play an important role in FFAs induced liver inflammation and injury.
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