Journal
PEERJ
Volume 4, Issue -, Pages -Publisher
PEERJ INC
DOI: 10.7717/peerj.1663
Keywords
CD14; TLR4; PUFA; Macrophages; Lipid rafts
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SCHU 2586/1-2]
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It is well known that PUFA impede the LPS-rnediated activation of the transcription factor NFkappaB. However, the underlying mode of action has not been clarified yet. To address this issue in a comprehensive approach, we used the monocyte/macrophage cell line RAVV264.7 to investigate the consequences of a PUFA supplementation on the TLR4 pathway with a focus on (i) the gene expression of TLR4 itself as well as of its dowrnstream mediators, (ii) the membrane microdomain localization of TLR4 and CD14, (iii) the stimulation -induced interaction of TLR4 and CD14. Our data indicate that the impairment of the TLR4-mediated cell activation by PUFA supplementation is not due to changes m gene expression of mediator proteins of the signaling cascade. Rather, our data provide evidence that the PUFA enrichment of macrophages affects the TLR4 pathway at the membrane level. PUFA incorporation into membrane lipids induces a reordering of membrane microdomains thereby affecting cellular signal transduction. It is important to note that this remodeling of macrophage rafts has no adverse effect on cell viability. flence, microdomain disruption via macrophage PUFA supplementation has a potential as non-toxic strategy to attenuate inflammatory signaling.
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