In addition to the robust intracellular
In addition to the robust intracellular calcium mobilisation, DHA and TUG-891 also induced MMP-9 granules release and superoxide production, supporting a key role of calcium in bovine neutrophil defense responses (Burgos et al., 2011). Pisani et al. (Pisani et al., 2009) described a reduction of basal extracellular ROS production in DHA-treated goat neutrophils, which would appear to conflict with our results at first glance; however, this discrepancy might be explained by differences in the study protocols such as the use of an assay of extracellular ROS measurement and time of the assay (30–120 min), because DHA at 30–40 min can be converted to 17S series resolvins by lipoxygenation, which are important mediators in resolution (Hong et al., 2003). In addition, this result could suggest the basal activation of neutrophils. Surprisingly, co-treatment of neutrophils with AH7614 and DHA or TUG-891 did not result in inhibition of MMP-9, and superoxide production was reduced by AH7614 only in the TUG-891-stimulated neutrophils. This result suggests that DHA could independently affect FFA4, although the mechanism remains to be elucidated. He (He et al., 2017) suggested that DHA reduced the lipopolysaccharide-stimulated inflammatory response in mammary epithelial Naproxen Sodium through a mechanism partly dependent on peroxisome proliferator-activated receptor gamma activation, and other studies have suggested that DHA produces changes in the physical-chemical properties of the membrane owing to the incorporation of DHA in lipid rafts (Corsetto et al., 2017; Schaefer et al., 2016).
Since AH7614 did not completely block the intracellular calcium mobilisation induced by DHA or TUG-891, it is possible that the remaining intracellular calcium could be sufficient to induce MMP-9 release, superoxide production, and other calcium-dependent responses in neutrophils. We confirmed that intracellular calcium is crucial for the superoxide production induced by FFA4 agonists because only BAPTA-AM (the intracellular calcium chelator) reduced this response, whereas MMP-9 release was not inhibited by either BAPTA-AM or EGTA (an extracellular calcium inhibitor), suggesting that other mechanisms could be more important in this response induced by FFA4 agonists. Moreover, different calcium pools are necessary to induce specific neutrophil responses. For example, oleic acid, an FFA1 agonist, was found to induce CD11b surface expression in an intracellular calcium-dependent manner, whereas oleic acid-induced MMP-9 release required extracellular calcium (Hidalgo et al., 2011).
Funding This work was supported by the Fondo Nacional de Desarrollo Científico y Tecnológico (Grant FONDECYT No. 1151047) and the Universidad Austral de Chile (Grant D-2018-01 VIDCA).
Introduction A dietary role has long been implicated in the etiology of cell proliferation, migration, and tumorigenesis in human cancers. An assortment of previous epidemiological and clinical studies have reported potential correlations between dietary fat intake and some cancers, and biochemical characterization in cell-based studies strongly support this linkage. Together, previous studies suggest that dietary factors can influence 30% of all cancers in Western nations . Dietary considerations, which can include ingestion of vitamins, grains, fiber, fruits, vegetables, meats, fats, alcohol, and sugars, have been linked to both progression of cancers, as in the case of meats, fats, alcohol, and sugars; as well as prevention of cancers, as in the case of grains, fiber, fruits, fats, and vegetables. Dietary nutrients have been suggested to influence overall cancer risk and progression of nearly all organ-based cancers including, colorectal , , , ovarian , , , , prostate , , lung , , , breast , , , and pancreatic , ,  cancers . It is now generally accepted that lifestyle, including diet, physical activity, and body weight are important contributors to cancer epidemiology.