Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via Toll-like receptor-2-mediated pathways
Autor: | Jay Whelan, Hui Wen Hsueh, Zhou Zhou, Hyojung Kim, Naima Moustaid-Moussa, Kenneth G.D. Allen, Kate J. Claycombe |
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Rok vydání: | 2011 |
Předmět: |
Lipopolysaccharides
medicine.medical_specialty MAP Kinase Signaling System Adipose tissue macrophages Medicine (miscellaneous) Adipose tissue Biological Transport Active Gene Expression Mice Obese Biology Models Biological Proinflammatory cytokine chemistry.chemical_compound Mice Adipocyte Internal medicine Fatty Acids Omega-3 medicine Adipocytes Animals Obesity RNA Messenger Unsaturated fatty acid Nutrition and Dietetics Interleukin-6 Stem Cells NF-kappa B ob/ob mouse Toll-Like Receptor 2 Mice Inbred C57BL TLR2 Endocrinology Interleukin-1 Receptor-Associated Kinases chemistry Eicosapentaenoic Acid lipids (amino acids peptides and proteins) Stem cell Signal Transduction |
Zdroj: | The Journal of nutrition. 141(7) |
ISSN: | 1541-6100 |
Popis: | Increased adipose tissue positively correlates with circulating inflammatory cytokines such as IL-6. We previously reported that adipose stem cells from genetically obese ob/ob mice produce significantly higher levels of IL-6 compared with other cell types such as adipocytes and macrophages within adipose tissue. We also demonstrated that (n-3) PUFA have antiinflammatory effects on adipocyte IL-6 secretion. Based on these findings, we hypothesized that EPA [20:5 (n-3)] and stearidonic acid [SDA, 18:4 (n-3)] would decrease LPS (200 μg/L)-induced IL-6 secretion and IL-6 mRNA content in the adipose stem cells. SDA (100 μmol/L) and EPA (100 μmol/L) significantly reduced LPS-induced IL-6 secretion and decreased IL-6 mRNA expression. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor (TLR) 4 and TLR2 expression were modulated by these fatty acids using Western-blot analysis. EPA and SDA suppressed LPS-induced TLR2 but not TLR4 protein expression in the adipose stem cells. Furthermore, SDA and EPA significantly lowered the activation and translocation of NF-κB, a TLR2 downstream signaling target, while protein expression of extracellular signal-regulated kinases-1/2 were unaffected. Collectively, our results suggest that EPA and SDA inhibit LPS-induced IL-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2-mediated signaling pathways. |
Databáze: | OpenAIRE |
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