Fatty acids as metabolic mediators in innate immunity
Article first published online: 26 JUN 2009
© 2009 The Authors. Journal Compilation © 2009 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 39, Issue 10, pages 924–933, October 2009
How to Cite
Kopp, A., Gross, P., Falk, W., Bala, M., Weigert, J., Buechler, C., Neumeier, M., Schölmerich, J. and Schäffler, A. (2009), Fatty acids as metabolic mediators in innate immunity. European Journal of Clinical Investigation, 39: 924–933. doi: 10.1111/j.1365-2362.2009.02185.x
- Issue published online: 15 SEP 2009
- Article first published online: 26 JUN 2009
- Received 26 March 2009; accepted 28 May 2009
- fatty acid;
Background Increasing data support the hypothesis of a local and systemic crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of this study was to characterize the immunomodulatory effects of a large panel of fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary human monocytes. We tested whether anti-inflammatory fatty acids are able to inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like receptor/MD-2 (TLR4/MD-2).
Materials and methods Resistin, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate the effect of fatty acids on binding of LPS to its receptor. In 30 patients with type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with LPS-induced monocyte activation was analysed.
Results Eleven fatty acids investigated exerted differential effects on the monocytic release of cytokines and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on human primary monocytes and THP-1 cells; 100 and 200 μM eicosapentaenoic acid dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of monocytic MCP-1 and TNF was significantly and positively correlated with serum triglyceride levels in 30 patients with T2D.
Conclusions Monocytic activation is differentially regulated by fatty acids and depends on triglyceride levels in T2D. The main finding of the present study shows that eicosapentaenoic acid inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid represents a new anti-inflammatory LPS-antagonist.