Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-κB and signal transducer and activator of transcription 3 pathways

Increasing evidence has demonstrated that mesenchymal stem cells (MSCs)-mediated regulation of macrophages is critical for inflammation response and tissue injury repair. However, the underlying mechanism is not well understood. In this study, we investigated the effect of mouse bone marrow-derived MSCs on macrophages under normal and inflammatory conditions. Coculture with MSCs or treatment with MSC-conditioned medium (MSC-CM) reduced the expression of tumor necrosis factor-alpha while inducing the expression of interleukin 10 (IL-10) and arginase 1 in lipopolysaccharide (LPS)-stimulated mouse RAW264.7 cells and splenic CD11b(+) cells. MSC-CM treatment increased the expression of CD206, a marker of alternatively activated M2 macrophages, in RAW264.7 cells. In addition, MSC-CM promoted the proliferation and migration of RAW264.7 cells. MSC-CM treatment activated signal transducer and activator of transcription 3 (STAT3) but inhibited nuclear factor-kappa B (NF-kappa B) pathways in LPS-stimulated RAW264.7 cells. Moreover, STAT3 inhibitor S3I-201 antagonized the induction of IL-10, arginase 1, and CD206 by MSC-CM in RAW264.7 cells. Conclusively, our findings suggest that mouse MSCs induce macrophage M2 activation through the NF-kappa B and STAT3 pathways.