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

Area of Science:

• Immunology
• Cancer Biology
• Molecular Biology

Background:

• The tumor microenvironment (TME) contains immune cells like tumor-associated macrophages (TAMs) that influence cancer.
• TAMs can promote tumor angiogenesis, metastasis, and proliferation.
• A mutated IL-32θ variant in breast cancer suppressed cancer cell migration and proliferation.

Purpose of the Study:

• To investigate the effects of recombinant human IL-32θ (rhIL-32θ) on macrophage polarization.
• To determine if rhIL-32θ influences TAMs within the tumor microenvironment.

Main Methods:

• Generated rhIL-32θ using an *Escherichia coli* expression system.
• Induced M0 macrophage polarization in THP-1 cells with PMA.
• Cultured M0 macrophages with IL-4/IL-13 (M2 induction) or rhIL-32θ.
• Analyzed M1 and M2 macrophage marker mRNA levels.
• Investigated the involvement of MAPK and NF-κB pathways.

Main Results:

• rhIL-32θ increased M1 macrophage markers (IL-1β, TNFα, iNOS) in M0 macrophages.
• rhIL-32θ decreased M2 macrophage markers (CCL17, CCL22, TGFβ, CD206) in M2 macrophages.
• rhIL-32θ induced NF-κB nuclear translocation via the MAPK (p38) pathway.

Conclusions:

• Point-mutated rhIL-32θ induces polarization towards M1-like macrophages.
• This polarization occurs through the MAPK (p38) and NF-κB (p65/p50) signaling pathways.
• rhIL-32θ's effect on macrophage polarization warrants further investigation in cancer therapy.