Several studies indicate that the n-3 long-chain
polyunsaturated fatty acid docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in the development of
neurodegenerative disorders, such as Alzheimer's and
Parkinson's disease. To explain these effects, different mechanisms are being proposed, including those involving
endocannabinoids and related signaling molecules. Many of these compounds belong to the
fatty acid amides, conjugates of
fatty acids with
biogenic amines. Conjugates of DHA with
ethanolamine or
serotonin have previously been shown to possess anti-inflammatory and potentially neuroprotective properties. Here, we synthesized another
amine conjugate of DHA,
N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in both RAW 264.7 macrophages and BV-2 microglial cells.
N-Docosahexaenoyl dopamine significantly suppressed the production of
nitric oxide (NO), the
cytokine interleukin-6 (IL-6), and the
chemokines macrophage-inflammatory protein-3α (CCL20) and
monocyte chemoattractant protein-1 (MCP-1), whereas its parent compounds,
dopamine and DHA, were ineffective. Further exploration of potential effects of DHDA on key inflammatory mediators revealed that
cyclooxygenase-2 (COX-2)
mRNA level and production of
prostaglandin E2 (
PGE2) were concentration-dependently inhibited in macrophages. In activated BV-2 cells,
PGE2 production was also reduced, without changes in COX-2
mRNA levels. In addition, DHDA did not affect
NF-kB activity in a reporter cell line. Finally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl
dopamine (NADA) and similar potencies were found in both cell types. Taken together, our data suggest that DHDA, a potentially endogenous
endocannabinoid, may be an additional member of the group of immune-modulating
n-3 fatty acid-derived
lipid mediators.