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

Biochem Biophys Res Commun. 2021 Dec 3;581:6-11. doi: 10.1016/j.bbrc.2021.10.010. Epub 2021 Oct 7.

Abstract

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-1β release. However, CD38 inhibition by 78c elevated intracellular NAD+ levels and suppressed IL-1β release in MSU crystals-treated THP-1 macrophages and BMDMs. Interestingly, CD38 inhibition without significant elevation of intracellular NAD+ also decreased IL-1β 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.

Keywords: CD38; Gout; Hyperuricemia; Inflammation; Monosodium urate crystals; Nicotinamide adenine dinucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / agonists
  • ADP-ribosyl Cyclase 1 / genetics*
  • ADP-ribosyl Cyclase 1 / metabolism
  • Animals
  • Crystallization
  • Female
  • Gene Expression Regulation
  • Gout / etiology
  • Gout / genetics
  • Gout / metabolism
  • Gout / pathology
  • Humans
  • Hyperuricemia / etiology
  • Hyperuricemia / genetics
  • Hyperuricemia / metabolism
  • Hyperuricemia / pathology
  • Inflammation
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Membrane Glycoproteins / agonists
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • NAD / metabolism
  • Primary Cell Culture
  • Signal Transduction
  • THP-1 Cells
  • Uric Acid / pharmacology*

Substances

  • IL1B protein, human
  • Interleukin-1beta
  • Membrane Glycoproteins
  • NAD
  • Uric Acid
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1