Transcriptomic Profiling Reveals That HMGB1 Induces Macrophage Polarization Different from Classical M1

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Macrophages are crucial immune cells with adaptable phenotypes.
• High-mobility group box 1 (HMGB1) influences macrophage polarization via TLR4, RAGE, and CXCR4.
• Understanding HMGB1's role in macrophage polarization is vital for inflammatory disease research.

Purpose of the Study:

• To investigate the impact of different HMGB1 redox isoforms on macrophage polarization.
• To analyze transcriptomic changes in murine bone-marrow-derived macrophages (BMDMs) stimulated with HMGB1 using RNA sequencing.
• To compare HMGB1-induced polarization with lipopolysaccharide (LPS)-induced polarization.

Main Methods:

• Murine bone-marrow-derived macrophages (BMDMs) were stimulated with disulfide HMGB1 (dsHMGB1) and fully reduced HMGB1 (frHMGB1).
• Bulk RNA sequencing (RNA-Seq) was employed to analyze transcriptomic profiles.
• Oil red O staining was used to assess foam cell formation.

Main Results:

• dsHMGB1 stimulation resulted in transcriptomic profiles distinct from LPS/IFNγ- and LPS-stimulated BMDMs.
• dsHMGB1-stimulated BMDMs exhibited enrichment in lipid metabolism and foam cell differentiation pathways.
• Both dsHMGB1 and frHMGB1 demonstrated a protective effect against oxidized low-density lipoprotein (oxLDL)-induced foam cell formation.

Conclusions:

• HMGB1 redox isoforms induce distinct macrophage polarization phenotypes.
• dsHMGB1 significantly impacts macrophage transcriptomics, particularly in lipid metabolism.
• HMGB1 may play a role in modulating foam cell formation, suggesting therapeutic potential.