FRI0511 LOW ω6-ω3 RATIOS CAUSED REDUCTION IN CELLULAR INFLAMMATION IN HUMAN SYNOVIOCYTES CELL LINE (SW982): GENE EXPRESSION STUDY
Authors: Abhay Harsulkar, Priya Kulkarni, Vanshika Srivastava, Ragini Vidya, Saurabh Yadav, Shreya Chitnavis, Alankruta Senapati
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Alarming global increase in osteoarthritis (OA), coupled with off target existing palliative care poses nutraceuticals an extremely attractive alternative in this respect. Beyond meeting the basic nutritional demands, nutrition is thought to play a beneficial role in the management of chronic diseases. Interestingly, the off target effects of nutriceuticals are beneficial in reducing co-morbidities. Skewed ratio of ω-6: ω-3 fatty acids (FAs) in modern diets has been shown associated with increased number of inflammatory diseases including bone and cartilage metabolism. Considering this, due to their disease modifying actions, ω-3 FAs are thought to serve better in OA management. <h3>Objectives</h3> We here investigated the effect of different ω-6: ω-3 ratios on synovitis, a prominent OA pathology. The selected ratios are generally found in global diet. <h3>Methods</h3> Selected ω-6FAs - arachidonic acid (AA), eicosadienoic acid (EDA), linolic acid (LA) and dihomo gamma linoleic acid (DGLA) along with selected ω-3 FAs docosapentaenoic acid 5 (DPA) and α-linolenic acid (ALA) were tested on induced SW-982 cells, in common dietary ratios of 16:1, 8:1, 4:1, 2:1 and 1:1 for their effect on synovial inflammation. For induction, 50ng/ml tumor necrosis factor-α (TNF-α) was used for 72 hrs and the PUFAs were added in the culture media in the selected ratios (concentration of each PUFA - 50μM). Finally, isolated cDNA was used to run quantitative RT-PCR for superoxide dismutase (SOD), interleukin-15 (IL-15), matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor (VEGF). <h3>Results</h3> All the ratios LA:ALA of caused a remarkable reduction in MMP-1(P&lt;0.001). Marginal reduction in VEGF was noted with1:1, 4:1 and 8:1 ratios (P&lt;0.005); 8:1 and 16:1 showed a significant increase (P&lt;0.001). SOD did not show any particular trend but noteworthy increase was observed with 2:1, 8:1 and 16:1 ratios (P&lt;0.001) while reduction with 1:1 and 4:1 ratios (P&lt;0.001). IL-15 remained low for 1:1, 2:1and 4:1 while a marked up-regulation was noted for 8:1 and 16:1 ratios (P&lt;0.001). In case of EDA:DPA, a consistent down-regulation of MMP-1was found with all the ratios excluding 4:1. The selected ratios were efficient against VEGF (P&lt;0.001). A consistent high SOD was revealed by all the ratios of EDA:DPA, which remained comparable to control. Marginal reduction in IL-15 was noted with 1:1, 8:1 and 16:1 (P&lt;0.05). Lastly, a significant MMP-1 reduction was caused by all the ratios of DGLA:DPA, except 2:1. Excluding 2:1, all the ratios were efficient against VEGF (P&lt;0.001). Increased levels of SOD remained comparable with TNF-α for 1:1 and 4:1; a trivial drop was noted with 2:1 and 8:1, followed by a noticeable reduction with 16:1. IL-15 showed a down-regulation with 1:1, 4:1, 8:1 ratios of DGLA: DPA. <h3>Conclusion</h3> Consequence of synovial inflammation in typical and atypical forms results in cartilage-loss, osteophytes and pain. FA ratios when used in equivalent, was found highly effective against IL 15, MMP1 and VEGF, whereas inflammation increases with increase in their proportions. Low SOD indicated lower oxidative-stress while it was up-regulated in response to high stress. FAs work in two distinct ways, membrane incorporation and metabolic modulation. Unsaturated fatty acid increase membrane fluidity and thus improves cell signaling. Analysis of treated and untreated cells showed incorporation of FAs in cell membrane, which improves membrane fluidity and status of signal transduction. <h3>Acknowledgement</h3> This research work has been carried out as a part of OAIBGE2016-18, an international consortium supported by INNO-INDIGO (EU-India multilateral research calls). Authors acknowledge EC of INNO-INDIGO for the funds. <h3>Disclosure of Interests</h3> None declared