UC San Diego

Gout is an inflammatory disease that is characterized by monosodium urate (MSU) crystal deposition in the joints, resulting in extreme pain and swelling. Although there are multiple anti-inflammatory therapies for gout, management of the disease can become difficult, since some anti-inflammatory drugs present many side effects and may be detrimental to individuals with comorbidities. Therefore, the discovery of a new anti-inflammatory therapeutic for gout is greatly needed. Inflammatory conditions are associated with the decline in nicotinamide adenine dinucleotide (NAD+). NAD+ is a fundamental cofactor for energy metabolism and cell function. NAD+ depletion could be due to numerous factors, such as precursor deficiency as well as NADase activity. Cluster of differentiation 38 (CD38) has been established as a proinflammatory surface marker on immune cells with NADase activity, which is the leading cause of NAD+ decline in mammalian tissues. This study investigates the role of CD38 in regulating MSU crystal-induced inflammation in murine bone marrow-derived macrophages (BMDMs) in vitro. MSU crystals were found to increase CD38 expression, causing a decrease in NAD/NADH ratio in BMDMs. However, CD38 inhibition by apigenin or genetic knockout of CD38 both increased the NAD/NADH ratio and attenuated the production of inflammatory cytokines induced by MSU crystals in BMDMs. These findings suggest that CD38 inhibition has the potential to be a novel therapeutic strategy for gouty inflammation.