Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumorassociated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32 0 was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32 0 on TAMs remain elusive. Recombinant human IL-32 0 (rhIL-32 0 ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32 0. The mRNA level of M1 macrophage markers (IL-1 ll, TNF a, inducible nitric oxide synthase) were increased by rhIL-32 0 in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGF ll, CD206) were decreased by rhIL-32 0 in M2 macrophages. rhIL-32 0 induced nuclear translocation of the NF- d 3 via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32 0 induced the polarization to M1like macrophages through the MAPK (p38) and NF- d 3 (p65/p50) pathways.