CCL2 promotes macrophages-associated chemoresistance via MCPIP1 dual catalytic activities in multiple myeloma.

ABSTRACT: We previously showed that the chemokine CCL2 can recruit macrophages (Mφs) to the bone marrow (BM) in multiple myeloma (MM) and that myeloma-associated Mφs are important in drug resistance. Here, we explore the role of increased CCL2 expression in the BM microenvironment of MM and elucidate the underlying mechanism. Our results show that CCL2 expression is associated with the treatment status of MM patients. Mφs interact with MM cells and further upregulate their expression of CCL2. These increased level of CCL2 polarizes Mφs toward the M2-like phenotype and promotes Mφs to protect MM cells from drug-induced apoptosis. Mechanistically, CCL2 upregulated the expression of the immunosuppressive molecular MCP-1-induced protein (MCPIP1) in Mφs. MCPIP1 mediates Mφs' polarization and protection v

SUBMITTER: Xu R 

PROVIDER: S-EPMC6791869 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature