Rat Anti-Mouse Macrophage Heterohybridoma [G5/91]

Riboflavin is commonly taken as a nutritional supplement, and it converts to coenzymes during the process of energy production from carbohydrates, fats, and proteins. Although riboflavin is considered to be an anti-inflammatory vitamin because of its antioxidant properties, the effects of riboflavin on inflammasome have been not reported. Inflammasome, a cytosolic surveillance protein complex, leads to the activation of caspase-1, cytokine maturation, and pyroptosis. In the present study, riboflavin attenuated the indicators of NLRP3 inflammasome activation in macrophages, such as the maturation and secretion of interleukin (IL)-1 beta, IL-18, and caspase-1; the formation of Asc pyroptosome; and the cleavage of gasdermin D. In addition, the oral and peritoneal administration of riboflavin inhibited the peritoneal production of IL-1 beta and IL-18 in a mouse model. Mechanistically, riboflavin prevented mitochondrial perturbations, such as mitochondrial ROS production and mitochondrial DNA release, which trigger the NLRP3 inflammasome assembly. Riboflavin was further confirmed to disrupt the activity of caspase-1, and it also inhibited the AIM2, NLRC4, and non-canonical inflammasomes. Therefore, riboflavin has both an antioxidant effect and an anti-inflammasome property that regulates the inflammatory response.

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.