CD38 activation by monosodium urate crystals contributes to inflammatory responses in human and murine macrophages

Cluster of differentiation (CD) 38, a major enzyme for nicotinamide adenine dinucleotide (NAD(+)) degradation, plays a key role in inflammation. Meanwhile, intracellular NAD+ decline is also associated with inflammatory responses. However, whether CD38 activation is involved in gouty inflammation has not been elucidated. The present study aimed to clarify the role of CD38 in monosodium urate crystals (MSU)-triggered inflammatory responses. The results showed that MSU crystals increased the protein expression of CD38 in time-and concentration-dependent manner in THP-1 macrophages and mouse bone marrow-derived macrophages (BMDMs). Moreover, intracellular NAD(+) levels were reduced by MSU crystals along with the increased IL-1 beta release. However, CD38 inhibition by 78c elevated intracellular NAD(+) levels and suppressed IL-1 beta release in MSU crystals-treated THP-1 macrophages and BMDMs. Interestingly, CD38 inhibition without significant elevation of intracellular NAD(+) also decreased IL-1 beta release driven by MSU crystals in THP-1 macrophages. In conclusion, the present study revealed that MSU crystals could activate CD38 with the ensuing intracellular NAD(+) decline to promote inflammatory responses in THP-1 macrophages and BMDMs, while CD38 inhibition could suppress MSU crystals-triggered inflammatory responses, indicating that CD38 is a potential therapeutic target for gout. (C) 2021 Elsevier Inc. All rights reserved.