Cellular uptake and anti-inflammatory effects of palm oil-derived delta (delta)-tocotrienol in microglia
CELLULAR IMMUNOLOGY
Authors: Tan, Shi Wei; Ali, Daud Ahmad bin Israf; Khaza'ai, Huzwah; Wong, Jia Woei; Vidyadaran, Sharmili
Abstract
Tocopherols long dominated studies on vitamin E, although interest has shifted to tocotrienols. It was previously shown that delta-tocotrienol derived from palm oil reduced nitric oxide released by BV2 microglia as early as 18 h after lipopolysaccharide stimulation. The current study measured delta-tocotrienol uptake by BV2 over a 24 h incubation period and its anti-inflammatory effects on primary microglia. Uptake of 17.5 mu g/mL delta-tocotrienol by BV2 microglia began as early as 5 min and rose steeply to 21 +/- 3% of the amount administered at 24 h. The amount of delta-tocotrienol retained in the lipopolysaccharide-stimulated microglia at 24 h was 14 +/- 2%, with no substantial difference seen in unstimulated microglia. The same delta-tocotrienol regimen reduced nitric oxide levels by 82% at 24 h after lipopolysaccharide stimulation (p < 0.05). This was accompanied by decreased inducible nitric oxide synthase protein expression by 67 +/- 5% compared to untreated controls (p < 0.05). In primary microglia, delta-tocotrienol downregulated IL-1 beta production, but TNF-alpha and IL-6 were not affected. delta-Tocotrienol also reduced prostaglandin E2 production by similar to 78%% and decreased transcription of COX-2 and 5-LOX, but not COX-1. This study showed the anti-inflammatory effects of delta-tocotrienol derived from palm oil and opens up interest for tocotrienol supplementation to reduce the effects of inflammatory conditions.
Key differences between olfactory ensheathing cells and Schwann cells regarding phagocytosis of necrotic cells: implications for transplantation therapies
SCIENTIFIC REPORTS
Authors: Nazareth, L.; Shelper, T. B.; Chacko, A.; Basu, S.; Delbaz, A.; Lee, J. Y. P.; Chen, M.; St John, J. A.; Ekberg, J. A. K.
Abstract
Transplantation of peripheral nervous system glia is being explored for treating neural injuries, in particular central nervous system injuries. These glia, olfactory ensheathing cells (OECs) and Schwann cells (SCs), are thought to aid regeneration by clearing necrotic cells, (necrotic bodies, NBs), as well as myelin debris. The mechanism by which the glia phagocytose and traffic NBs are not understood. Here, we show that OECs and SCs recognize phosphatidylserine on NBs, followed by engulfment and trafficking to endosomes and lysosomes. We also showed that both glia can phagocytose and process myelin debris. We compared the time-course of glial phagocytosis (of both NBs and myelin) to that of macrophages. Internalization and trafficking were considerably slower in glia than in macrophages, and OECs were more efficient phagocytes than SCs. The two glial types also differed regarding their cytokine responses after NB challenge. SCs produced low amounts of the pro-inflammatory cytokine TNF-alpha while OECs did not produce detectable TNF-alpha. Thus, OECs have a higher capacity than SCs for phagocytosis and trafficking, whilst producing lower amounts of pro-inflammatory cytokines. These findings suggest that OEC transplantation into the injured nervous system may lead to better outcomes than SC transplantation.