title: Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.
abstract: 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 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα 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 PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα 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 PPARα signaling, inhibiting the TLR4-mediated NF-κB 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.
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Yang
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Xiamen Medical College, Xiamen, Fujian, 361008, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Meng
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, P. R. China.
authors.lastname: Dan Zhang
authors.affiliation: Xiamen Cancer Center, Department of Radiation Oncology, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, P. R. China.
authors.forename: Sangang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, P. R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiamen, Fujian, 361102, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009829:Oleic Acids / Q000494:pharmacology*; D047493:PPAR alpha / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000074084:THP-1 Cells; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009829:Oleic Acids; C440229:Oleylethanolamide; D047493:PPAR alpha; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018808:Transcription Factor AP-1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3