Interleukin-10 increases macrophage-mediated chemotherapy resistance via FABP5 signaling in multiple myeloma

• Published in: International immunopharmacology Vol. 124; p. 110859
• Main Authors: Zhang, Mingyue, Chen, Jintong, Zhang, Hua, Dong, He, Yue, Ying, Wang, Siqing
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2023
• Subjects: Chemotherapy resistance; FABP5; Interleukin-10; Macrophage; Multiple myeloma; Chemotherapy resistance; Interleukin-10; FABP5; Multiple myeloma; Macrophage
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110859

•IL-10 increased macrophage-induced multiple myeloma chemotherapy resistance.•IL-10 enhanced lipid accumulation and β-oxidation in macrophages.•IL-10 enhanced macrophage-mediated myeloma chemotherapy resistance via FABP5.•Targeting FABP5 signaling has potentially important clinical implications. Macrophages (MΦs) protect multiple myeloma (MM) cells from chemotherapy-induced apoptosis, and interleukin-10 (IL-10) is frequently elevated in the MM microenvironment. However, the role of IL-10 in MΦ-induced tumor chemotherapy resistance has not yet been clarified. In the present study, bone marrow-derived MΦs were treated with IL-10 (IL10-MΦs), and IL10-MΦ-induced MM chemotherapy resistance was evaluated. IL-10 promoted MΦ-mediated resistance to MM chemotherapy. In addition, IL-10 treatment increased lipid accumulation and fatty acid β-oxidation in MΦs. Mechanistically, IL-10 increased fatty acid binding protein 5 (FABP5) expression in MΦs, and targeting FABP5 decreased MM chemotherapy resistance induced by IL10-MΦs in vitro and enhanced chemotherapeutic efficacy in vivo. Inhibition of FABP5 decreased the expression of Carnitine Palmitoyltransferase 1A (CPT1A) in IL10-MΦs. In addition, inhibition of CPT1A in IL10-MΦs decreased IL10-MΦ-mediated MM chemotherapy resistance. Peroxisome proliferator-activated receptor γ (PPARγ) is upstream of FABP5 signaling. Inhibition of PPARγ in IL10-MΦs decreased IL10-MΦ-mediated MM chemotherapy resistance in vitro. Collectively, our work indicates that IL-10 enhances MΦ-mediated MM chemotherapy resistance via FABP5 signaling and targeting FABP5 has potentially important clinical implications.