Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity.
Bottom Line: Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity.These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.
Affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. firstname.lastname@example.orgShow MeSH
Related in: MedlinePlus
Mentions: To explore further the effect of GTAs on modulating inflammation, we employed the RAW264.7 mouse macrophage line in which a pro-inflammatory state can be induced by treatment with lipopolysaccharide (LPS). RAW264.7 cells were treated for 4 hours with GTA+ve and GTA-ve fractions prior to the addition of LPS, and the effects on various proinflammatory markers evaluated. We observed no affect on RAW264.7 cell growth or proliferation rates during the 20 hours post-GTA treatment. RAW264.7 cells treated with GTA+ve fractions prior to LPS stimulation showed a significant dose-dependent reduction (p < 0.05) in the generation of nitric oxide as assessed through the production of nitrite using the Griess reagent system (Figure 6A), which was mirrored by low levels of NOS2 mRNA transcripts (Figure 6B) and protein levels (Figure 6C). For comparison (and as controls), cells were also treated with various combinations of free fatty acids including EPA, DHA and equimolar mixtures of 18:1, 18:2 and 18:3 (FA mix), of which only 100 uM DHA showed any protective effect on NOS2 protein induction (Figure 6C).
Affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. email@example.com