Immune Netw.  2024 Jun;24(3):e27. 10.4110/in.2024.24.e27.

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

• Park HM
• Park JY
• Kim NY
• Kim H
• Kim HG
• Son DJ
• Hong JT
• Yoon DY

• KMID: 2557911
• DOI: http://doi.org/10.4110/in.2024.24.e27

Abstract

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-32θ 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-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) 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-32θ. The mRNA level of M1 macrophage markers (IL-1β, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFβ, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Keyword

IL-32θ; Inflammation; Tumor microenvironment; Tumor-associated macrophages; Immunotherapy