Oleoylethanolamide Exerts Anti-Inflammatory Effects On Lps-Induced Thp-1 Cells By Enhancing Ppar Alpha Signaling And Inhibiting The Nf-Kappa B And Erk1/2/Ap-1/Stat3 Pathways

The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 mu g/ml) in the presence or absence of OEA (10, 20 and 40 mu M). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPAR alpha small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPAR alpha expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPAR alpha and TLR4. Importantly, OEA inhibited LPS-induced NF-kappa B activation, I kappa B alpha degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARa signaling, inhibiting the TLR4-mediated NF-kappa B signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.