Effects of EPA and DHA on proliferation, cytokine production, and gene expression in Raji cells.

The effects of EPA and DHA on the function and gene expression of a B-lymphocyte cell line (Raji) were investigated. Proliferation; production of interleukin-10 (IL-10), tumor necrosis factor (TNF)-alpha, and interferon (INF)-gamma; and expression of pleiotropic genes were evaluated. Cell proliferation was increased in the presence of 12.5 microM EPA (approximately twofold) and 12.5 microM DHA (approximately 1.5-fold). EPA and DHA (25 microM) also decreased production of the key immunoregulatory cytokines IL-10, TNF-alpha, and INF-gamma. EPA and DHA changed the expression of specific genes, but this effect was more marked for EPA (25.9% of genes investigated) compared with DHA (8.4% of genes investigated). EPA and DHA affected the expression of genes clustered as: cytokines, signal transduction, transcription, cell cycle, defense and repair, apoptosis, cell adhesion, cytoskeleton, and hormones. The most remarkable changes were observed in the genes of signal transduction and transcription. These results led us to conclude that the mechanism of DHA and EPA effects on B-lymphocyte functions includes regulation of gene expression. Thus, the ingestion of fish oil, a rich source of EPA and DHA, may have a strong effect on B-lymphocyte function in vivo. However, remarkable differences were observed between DHA and EPA, demonstrating that specific effects of these FA may be responsible for the marked differences in edible oil effects on immune function in vivo reported by others.