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

Mingyue Zhang; Jintong Chen; Hua Zhang; He Dong; Ying Yue; Siqing Wang

doi:10.1016/j.intimp.2023.110859

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

Int Immunopharmacol. 2023 Nov;124(Pt A):110859. doi: 10.1016/j.intimp.2023.110859. Epub 2023 Sep 2.

Authors

Mingyue Zhang¹, Jintong Chen², Hua Zhang³, He Dong¹, Ying Yue⁴, Siqing Wang⁵

Affiliations

¹ Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun 130061, China.
² Department of Cancer Immunology, The First Hospital of Jilin University, Changchun 130061, China.
³ Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130021, China.
⁴ Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun 130061, China. Electronic address: yuey@jlu.edu.cn.
⁵ Department of Cancer Immunology, The First Hospital of Jilin University, Changchun 130061, China. Electronic address: wkerger@jlu.edu.cn.

PMID: 37666065
DOI: 10.1016/j.intimp.2023.110859

Abstract

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.

Keywords: Chemotherapy resistance; FABP5; Interleukin-10; Macrophage; Multiple myeloma.