Shireen Al-Asfoor (Oman)
Imperial College London National Heart & Lung InstituteAuthor Of 1 Presentation
O036 - Differential Effects of Omega-3 Fatty Acids on Lipopolysaccharide (LPS)-induced Macrophage Activation in Combination with COX inhibition (ID 138)
Abstract
Background and Aims
Macrophages contribute to chronic diseases by promoting inflammation. Macrophage activation results in increased inducible nitric oxide synthase (iNOS) expression which can be modulated by cyclooxygenase (COX) activity. As both a substrate and potential inhibitor of COX activity, the omega-3 fatty acid EPA may modulate iNOS activity. We investigated the effect of EPA and DHA on iNOS activity in LPS-activated macrophages.
Methods
Murine J774 macrophages were pretreated with vehicle, EPA or DHA over a range of concentrations (1.9µM-50µM) during a challenge with lipopolysaccharide (LPS) at 1.0 µg/ml in DMEM supplemented with 1% FCS. After 24 hr, iNOS activity was assessed by nitrite production using the Griess assay. As a positive control, nitrite measurements with EPA and DHA were compared in combination with the COX inhibitor diclofenac at 100 µM.
Results
Macrophage treatment with LPS increased nitrite levels. EPA treatment reduced LPS-induced nitrite production in a concentration-dependent manner with statistically significant reductions (Figure 1). The inhibitory effects of EPA on iNOS activity were significantly (p<0.0001; two-way ANOVA with Sidak’s multiple comparisons test, n=9) enhanced at all concentrations in the presence of diclofenac. By contrast, DHA did not significantly reduce LPS induced iNOS activity either in the absence or presence of diclofenac.
Conclusions
Our observations that EPA but not DHA reduced macrophage iNOS activity may contribute to our understanding of the reduced cardiovascular events as reported in the REDUCE-IT trial with an EPA only formulation. The ability of EPA to modulate macrophage activity has therapeutic implications for patients with cardiovascular risk.
Presenter of 1 Presentation
O036 - Differential Effects of Omega-3 Fatty Acids on Lipopolysaccharide (LPS)-induced Macrophage Activation in Combination with COX inhibition (ID 138)
Abstract
Background and Aims
Macrophages contribute to chronic diseases by promoting inflammation. Macrophage activation results in increased inducible nitric oxide synthase (iNOS) expression which can be modulated by cyclooxygenase (COX) activity. As both a substrate and potential inhibitor of COX activity, the omega-3 fatty acid EPA may modulate iNOS activity. We investigated the effect of EPA and DHA on iNOS activity in LPS-activated macrophages.
Methods
Murine J774 macrophages were pretreated with vehicle, EPA or DHA over a range of concentrations (1.9µM-50µM) during a challenge with lipopolysaccharide (LPS) at 1.0 µg/ml in DMEM supplemented with 1% FCS. After 24 hr, iNOS activity was assessed by nitrite production using the Griess assay. As a positive control, nitrite measurements with EPA and DHA were compared in combination with the COX inhibitor diclofenac at 100 µM.
Results
Macrophage treatment with LPS increased nitrite levels. EPA treatment reduced LPS-induced nitrite production in a concentration-dependent manner with statistically significant reductions (Figure 1). The inhibitory effects of EPA on iNOS activity were significantly (p<0.0001; two-way ANOVA with Sidak’s multiple comparisons test, n=9) enhanced at all concentrations in the presence of diclofenac. By contrast, DHA did not significantly reduce LPS induced iNOS activity either in the absence or presence of diclofenac.
Conclusions
Our observations that EPA but not DHA reduced macrophage iNOS activity may contribute to our understanding of the reduced cardiovascular events as reported in the REDUCE-IT trial with an EPA only formulation. The ability of EPA to modulate macrophage activity has therapeutic implications for patients with cardiovascular risk.