Abstract
Olive oil contains high amounts of oleic acid (OA). Although OA has been described to inhibit inflammatory processes, the effects of olive oil on cellular mechanisms remain poorly understood. Therefore, we compared the effects of major fatty acids (FA) from olive oil with those of olive oil extracts (OOE) on inflammatory mediators and alterations in the cellular phospholipid composition in murine macrophages. Upon treatment with different OOE, FA compositions of lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages were analyzed using gas chromatography. Olive oil extracts and OA significantly reduced the LPS-induced expression of inducible nitric oxide synthase (iNos), cyclooxygenase (Cox2), and interleukin-6 mRNA. In addition, a significant decrease in Cox2 and iNos protein expression was observed. The formation of nitric oxide was significantly reduced, while the formation of prostaglandin (PG) E2 from arachidonic acid significantly increased after treatment with OOE or OA. The latter was associated with a shift in the phospholipid FA composition from arachidonic acid to OA, resulting in an elevated availability of arachidonic acid. Together, OOE and OA mediate anti-inflammatory effects in vitro but increase the release of arachidonic acid and hereinafter PGE2, likely due to elongation of OA and competitive incorporation of fatty acids into membrane phospholipids.
Highlights
The Mediterranean diet is characterized by high consumption of vegetables, fruits, nuts, and extra virgin olive oil (EVOO) and has been proposed to be protective against a broad range of diseases [1–3]
We comparatively studied the effects of an olive oil extracts (OOE), consisting of the lipophilic fraction of EVOO and fatty acids (FA), on the inflammatory response in LPS-induced RAW264.7 macrophages
While the LPS-induced expression of Tnfα was significantly reduced to 39% ± 7% (p < 0.01) by OOE and 47% ± 21%, even though just tendentially (p = 0.07), by oleic acid (OA) (Figure 1A), the effects for Il1β tended to be blocked to 47% ± 14% (p = 0.08) by OOE and to 54% ± 16% (p = 0.14) by OA (Figure 1B)
Summary
The Mediterranean diet is characterized by high consumption of vegetables, fruits, nuts, and extra virgin olive oil (EVOO) and has been proposed to be protective against a broad range of diseases [1–3]. The association between cardiovascular diseases and atherosclerosis, a chronic inflammatory disease, has been widely studied [4,5]. Macrophages play a pivotal role by secreting both pro- and anti-inflammatory mediators [6]. The aim of the inflammatory reaction is the elimination of the initial cause itself and the restoration of physiological homeostasis. Numerous regulatory factors participate that promote or resolve inflammation [7]. Typical immunomodulatory signaling molecules released by activated macrophages are cytokines, such as proinflammatory tumor necrosis factor (Tnf) α, interleukin (Il) 1β and 6, and anti-inflammatory Il10 [8,9]. Inflammatory stimuli lead to an activation of cyclooxygenase (Cox) 2 and inducible nitric oxide synthase (iNos) [10,11]. While the inducible isoform Cox generates proinflammatory eicosanoids, such as prostaglandin (PG) E2, iNos catalyzes the formation of the second messenger nitric oxide
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