Effect Of Acylated Ghrelin On The Activation Of TLR4/NF-κB Signaling Pathway In THP-1Macrophages Induced By Palmitic Acid

Objective:To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages.Methods:THP-1macrophages were cultured for12h by palmitic acid with various concentrations. Pretreatment of the THP-1macrophages with acylated ghrelin at different doses for4h before palmitic acid (200μmol/L) cultivation for12h. We observed the level of TLR4and NF-κB p65phosphorylation in THP-1macrophages and the expression of TNF-a and IL-1β in culture supernatant. TLR4mRNA was measured by Real-time PCR. The level of TLR4protein and NF-κB p65phosphorylation was measured by western blotting. The expression of TNF-a and IL-1β were detected by ELISA.Results:Compared to the THP-1macrophages without palmitic acid, the level of TLR4mRNA and protein and NF-κB p65phosphorylation, the expression of TNF-a and IL-1β were increased after treatment by palmitic acid in a dose-dependent fashion(P<0.05). Compared to the THP-1macrophages with palmitic acid (200μmol/L), the level of TLR4mRNA(P<0.05), the level of TLR4protein and NF-κB p65phosphorylation (P<0.01), the expression of TNF-α(P<0.05) and IL-1β (P<0.01) were decreased after preadministration by acylated ghrelin in a dose-dependent fashion. Conclusions:①Palmitic acid can regulate the activation of TLR4/NF-κB signaling pathway and induce the release of inflammatory cytokines in THP-1macrophages in a dose-dependent fashion.②Acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1macrophages which is stimulated by palmitic acid in a dose-dependent fashion.