I14 Metabolic regulation of IL-1beta transcription

In the field of inflammation research, the most important advances in the past 10 years has been in the uncovering of multiple pathways involved in innate immunity. The best characterised involve the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). From work on Nlrp3 there has also been a resurgence of interest in the IL1 system as a key driver of inflammation in diseases such as gout and diabetes (both Type I and Type II). Glucose has also been shown to drive IL-1beta production in beta cells in the pancreas. We have uncovered a process whereby glucose metabolism is required for induction of IL-1beta mRNA. We have evidence that this could involve the transcription factor HIF-1alpha which is stabilised by LPS in a process involving induction of succinate. The role of metabolic processes including glycolysis in the regulation of signalling in inflammation is also likely to be important here. The so-called Warburg effect of aerobic glycolysis is a feature of cells activated during inflammation (including Th17 cells) providing an added level of complexity to signalling pathways activated by TLRs during inflammation.