Butyrate, through a cAMP-dependent mechanism, promotes the gene expression involved in intestinal gluconeogenesis
It stimulates the synthesis of key ECM components, including collagen I and III, elastin, and various glycosaminoglycans (GAGs), by signaling through pathways such as the TGF-/SMAD cascade
B12 is essential for the normal function of immune cells, and deficiency has been associated with impaired immune responses
INO, derived from ADO or IMP via ADA, has context-dependent immune effects ( These ectoenzymes, expressed by resident cells ( Figure 1 ), which sequentially generates ADPR, AMP, and ultimately immunosuppressive ADO ( Based on this background, we hypothesized that the dual role of CD38as a catalytic signaling receptor and a key component of the adenosinergic networkcontributes to immune dysregulation in MM ( In vitro assays using DARA and ISA were performed on primary MM cells ( + consumption and production of cADPR and ADPR, the latter entering the CD203a/CD73 axis to generate ADO, a mechanism we previously demonstrated using co-culture models ( 2 Materials and methods 2.1 Myeloma cells The LP-1 (CD38 + /CD203a /CD73 ) and BF01 (CD38 + /CD203a + /CD73 ) myeloma cell lines were established from patients with plasma cell leukemia ( Primary MM plasma cells were isolated from BM aspirates by immunomagnetic separation using anti-CD138 monoclonal antibody-coated microbeads (Miltenyi Biotec, Bergisch Gladbach, Germany) ( 2.2 Cells and microvesicle phenotypes Surface molecule expression on LP-1 and BF01 MM cell lines, primary human BM mononuclear cells, and primary MM cells was analyzed as previously described ( + /CD38 + /CD203a - /CD26 + ), maintained in IMDM medium supplemented with 10% FCS (Hyclone), 2 mM L-glutamine and antibiotics
