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
Autor: | Lu Yan, Xianglan Meng, Hao Zhou, San-Gang Wu, Xin Jin, Ying Li, Qiang Xie, Lu Peng, Han Guo, Dan Zhang, Lichao Yang |
---|---|
Rok vydání: | 2016 |
Předmět: |
Lipopolysaccharides
STAT3 Transcription Factor 0301 basic medicine medicine.medical_specialty Lipopolysaccharide MAP Kinase Signaling System THP-1 Cells Oleic Acids Inflammation Pharmacology Article 03 medical and health sciences chemistry.chemical_compound Oleoylethanolamide Internal medicine medicine Humans PPAR alpha STAT3 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Multidisciplinary biology Anti-Inflammatory Agents Non-Steroidal NF-kappa B NF-κB Transcription Factor AP-1 IκBα 030104 developmental biology Endocrinology chemistry biology.protein TLR4 lipids (amino acids peptides and proteins) Signal transduction medicine.symptom |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep34611 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |