We explored how docosahexaenoic acid (DHA), a marine omega-3 fatty acid, impacts fibroblast-like synovial cells from patients with rheumatoid arthritis (RA). In our investigation, we found that DHA treatment triggered cell death in these cells through a process called apoptosis—a form of programmed cell death— and this effect increased with higher doses of DHA.
DHA not only induced apoptosis but also reduced the levels of proteins associated with inflammation, specifically MMP-9 and IL-1β. Interestingly, we observed that DHA prompted the activation of stress markers in the cells, indicating a response to abnormal stress conditions. Two key players in this process were identified: CHOP and death receptor 5 (DR5). When we reduced the expression of CHOP or DR5, the cells showed improved survival and less apoptosis, highlighting their roles in this pathway.
Additionally, DHA led to an increase in reactive oxygen species (ROS), compounds that can cause damage to cells. By using an antioxidant called Tiron, we discovered that it could prevent the effects of DHA, including the induction of CHOP and DR5, and reduce the cell death triggered by DHA. This protective effect boosted cell viability and diminished markers typically associated with apoptosis.
All of our findings in the lab were corroborated by results from human primary synovial cells from RA patients. This suggests that DHA may hold promise as a therapeutic agent for RA by harnessing oxidative stress and CHOP to promote cell death in the inflamed tissues of the joints.