The multi-faceted role of NADPH in regulating inflammation in activated myeloid cells
Kenneth Ting, Jenny Jongstra‐Bilen, Myron I. Cybulsky
Abstract
Recent advances in the immunometabolism field have demonstrated the importance of metabolites in fine-tuning the inflammatory responses in myeloid cells. Cofactors, which are metabolites comprised of inorganic ions and organic molecules, may tightly or loosely bind to distinct sites of enzymes to catalyze a specific reaction. Since many enzymes that mediate inflammatory and anti-inflammatory processes require the same cofactors to function, this raises the possibility that under conditions where the abundance of these cofactors is limited, inflammatory and anti-inflammatory enzymes must compete with each other for the consumption of cofactors. Thus, this competition may reflect a naturally evolved mechanism to efficiently co-regulate inflammatory versus anti-inflammatory pathways, fine-tuning the extent of an inflammatory response. The role of NADPH, the reduced form of nicotinamide adenine dinucleotide phosphate (NADP + ), in mediating inflammatory and anti-inflammatory responses in activated myeloid cells has been well-established in the past decades. However, how the dynamic of NADPH consumption mediates the co-regulation between individual inflammatory and anti-inflammatory pathways is only beginning to be appreciated. In this review, we will summarize the established roles of NADPH in supporting inflammatory and anti-inflammatory pathways, as well as highlight how the competition for NADPH consumption by these opposing pathways fine-tunes the inflammatory response in activated myeloid cells.