Sulforaphane diminishes moonlighting of pyruvate kinase M2 and interleukin 1β expression in M1 (LPS) macrophages.
Level 5 - mechanism / opinion, no new human data
In vitro bench study in murine cell cultures
PubMed 35983049 · doi:10.3389/fimmu.2022.935692
What was done
Investigated the mechanisms by which sulforaphane (Sfn) modulates lipopolysaccharide (LPS)-induced M1 activation in murine macrophages. The authors assessed proinflammatory markers (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS), cellular bioenergetics (aerobic glycolysis and respiration via extracellular flux analysis), and the oligomerization, glutathionylation, and subcellular localization of pyruvate kinase M2 (PKM2), along with downstream signaling intermediaries (HIF-1α and Stat3 phosphorylation).
What was found
The abstract reports directional changes without quantitative values. Sfn decreased M1 inflammatory markers (IL-1β, IL-6, TNF-α, iNOS, NO, ROS) and promoted high concurrent glycolytic and respiratory activity. Sfn prevented LPS-induced PKM2 glutathionylation, reduced PKM2 mono/dimerization and nuclear accumulation, and decreased HIF-1α levels and Stat3 tyrosine-705 phosphorylation, while preserving cytosolic PKM2 tetramers and high glycolytic enzyme activity.
Why it matters
Reveals PKM2 as a direct mechanistic hub for sulforaphane's anti-inflammatory actions, showing that Sfn can decouple high glycolytic activity from inflammatory gene expression by blocking PKM2 nuclear translocation.
Limits
The study is limited to in vitro murine macrophage models, precluding direct extrapolation to human in vivo inflammatory states or clinical pharmacokinetics. No exact sample sizes, replicate counts, or quantitative effect sizes were reported in the abstract.
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