CD38 Inhibition Attenuates Monosodium Urate Crystal-induced Inflammation in Macrophages
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.