Lipopolysaccharide Induces CD38 Expression and Solubilization in J774 Macrophage Cells

Abstract

*CD38, an ADP ribosyl cyclase, is a 45 kDa type II transmembrane protein having a short N-terminal cytoplasmic domain and a long C-terminal extracellular domain, expressed on the surface of various cells including macrophages, lymphocytes, and pancreatic β cells. It is known to be involved in cell adhesion, signal transduction and calcium signaling. In addition to its transmembrane form, CD38 is detectable in biological fluids in soluble forms. The mechanism by which CD38 is solubilized from the plasma membrane is not yet clarified. In this study, we found that lipopolysaccharide (LPS) induced CD38 upregulation and its extracellular release in J774 macrophage cells. Furthermore, it also increased CD38 expression at the mRNA level by activating the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway. However, LPS decreased the levels of CD38 in the plasma membrane by releasing CD38 into the culture supernatant. LPS-induced CD38 release was blocked by the metalloproteinase-9 inhibitor indicating that MMP-9 solubilizes CD38. In conclusion, the present findings demonstrate a potential mechanism by which C38 is solubilized from the plasma membrane.

CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma

“…In this study, mitochondria were shown to move in microvesicles, which enabled the restoration of metabolic potential and survival of neurons after stroke, and this process was shown to be dependent on CD38. Others have shown that lipopolysaccharide induces mitochondrial transfer from BMSC to alveoli (17), and lipopolysaccharide can induce CD38 upregulation (45). We further present that mitochondrial transfer in multiple myeloma is via a CD38dependant mechanism, independent of microvesicle transfer.…”

CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism

“…We and others have previously shown that lipopolysaccharides (LPS) and inflammatory cytokines such as TNF-α are potent inducers of CD38 expression in cells (Barata et. al., 2004; Lee et. al., 2012).…”

NAD and the aging process: Role in life, death and everything in between

“…CD38 expression and activity are induced by cytokines and bacterial endotoxins such as lipopolysaccharides (LPS) (Lee et al, 2012; Musso et al, 2001; Sun et al, 2006, Yamamoto-Katayoma et al, 2002). Thus, the chronic inflammation observed during aging could lead to an increase in expression of CD38 and subsequently cause NAD decline (Figure 4 and 5).…”