Emerging research highlights how the redox state of High Mobility Group Box 1 (HMGB1) influences macrophage behavior and function. The study, investigating murine bone-marrow-derived macrophages (BMDMs), reveals distinct effects of HMGB1 redox isoforms:
- Disulfide HMGB1 (dsHMGB1) induces a unique pro-inflammatory macrophage phenotype characterized by cytokine secretion without the metabolic reprogramming associated with nitric oxide production in classically acetivate M1 macrophages.
- Reduced HMGB1 (frHMGB1) does not induce macrophage polarization but retains the ability to promote cellular migration.
Both dsHMGB1 and frHMGB1 stimulate macrophage motility, demonstrating that HMGB1-mediated migration and inflammatory polarization are distinct biological responses.
These findings challenge the traditional M1/M2 classification by demonstrating that HMGB1 can induce an inflammatory macrophage phenotype that is functionally distinct from classical M1 activation.
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