The Effects of Omega-3 Polyunsaturated Fatty Acids on TNF-α and IL-10 Secretion by Murine Peritoneal Cells In Vitro

Omega-3 polyunsaturated fatty acids (PUFA) affect immune response, partly by affecting cytokine secretion. Omega-3 PUFA decrease tumor necrosis factor (TNF)-α secretion by RAW 264.7 macrophages but increase TNF-α secretion by primary elicited peritoneal macrophages in vitro. In this study, the effects of omega-3 and omega-6 PUFA on lipopolysaccharide induced TNF-α and interleukin (IL)-10 secretion by murine primary resident and elicited peritoneal macrophages and by RAW 264.7 macrophages, were examined in vitro using an enzyme-linked immunosorbent assay. In addition, the effects of dietary omega-3 PUFA on the number of cells secreting these cytokines were examined with enzyme-linked immunospot assay. All cell types secreted more TNF-α but similar amounts of IL-10 when incubated with the omega-3 PUFA, eicosapentaenoic acid or docosahexaenoic acid, compared with that when incubated with the omega-6 PUFA, linoleic acid or arachidonic acid. Dietary fish oil did not affect the number of TNF-α secreting resident peritoneal macrophages but decreased the number of macrophages secreting IL-10 ex vivo. These results show that dietary omega-3 PUFA and omega-3 PUFA added to cells in vitro increase TNF-α secretion by resident peritoneal macrophages, probably by a direct effect on the cells. In contrast, omega-3 PUFA did not affect IL-10 secretion by the cells but decreased the number of cells secreting IL-10 ex vivo, possibly by affecting cell recruitment, maturation or proliferation.     

Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC1-α). PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.