Condition Focus: Macrophage M1 Suppression — Notch1-HIF-1α-NF-κB Pathway

This study from Ma and colleagues provides the third independently identified signalling pathway through which PBM modulates macrophage polarization. Using RNA sequencing — which captures gene expression changes across the entire genome — the researchers demonstrated that PBM suppresses M1 macrophage activation through the Notch1-HIF-1α-NF-κB axis.

The pathway works as follows: Notch1 signalling, when activated in inflammatory macrophages, stabilises HIF-1α (hypoxia-inducible factor 1α), which in turn activates NF-κB — the master transcription factor for inflammatory gene expression. PBM suppresses this entire cascade, reducing IL-1α and IL-6 production by M1 macrophages.

While this study used a spinal cord injury model, the macrophage biology is universal. M1 macrophages in a gouty joint use the same Notch1-HIF-1α-NF-κB signalling as M1 macrophages anywhere else in the body. The pathway is particularly relevant to gout because HIF-1α is activated by hypoxia — and inflamed joints are hypoxic environments. The swelling and vascular congestion during a gout flare reduce oxygen delivery to the joint tissue, creating exactly the conditions where HIF-1α drives macrophage activation.

The RNA-seq confirmation means this is not a hypothesis based on measuring a few selected proteins. It is a genome-wide observation that PBM comprehensively suppresses the M1 inflammatory programme at the transcriptional level.

G.O.A.T. for Gout Alignment:
The Notch1-HIF-1α-NF-κB pathway adds a third confirmed mechanism to PBM’s macrophage modulation toolkit. The NF-κB component is the same transcription factor suppressed by 30% in inflamed tissues (per the Immunomodulatory Effects review). The G.O.A.T.’s application during acute flares — when joint hypoxia activates HIF-1α — targets this pathway at its most active.

Link to original research here

Editor’s note: This is the third mapped macrophage pathway, complementing PI3K/AKT/mTOR in Tian et al 2023 and IL-6/JAK/STAT in PBM and Chondrocyte Catabolism 2025. The NF-κB suppression component connects to Chen et al 2011 and Immunomodulatory Effects 2025. For wavelength-specific effects on macrophage markers, see Fernandes et al 2019.

Related Articles

• PBM Increases M2 Macrophages via PI3K/AKT/mTOR at 980nm – Tian et al 2023
• PBM Mitigates Chondrocyte Catabolism via Macrophage M1 Polarization – 2025
• PBM Activates NF-κB via Mitochondrial ROS at 810nm – Chen et al 2011
• Wavelength and Timing in PBM-Induced Macrophage Polarization – Fernandes et al 2019
• PBM and Macrophage Polarization: M1→M2 Shift Review – 2025

Key Takeaways

• Third mapped pathway for PBM macrophage modulation: Notch1-HIF-1α-NF-κB
• RNA-seq provides genome-wide confirmation of M1 programme suppression
• HIF-1α relevance: inflamed joints are hypoxic — activating exactly this pathway during gout flares
• NF-κB suppression connects to the central inflammatory transcription factor in gout

Study Overview

Citation

Ma Y, et al. (2022). Photobiomodulation attenuates neurotoxic polarization of macrophages by inhibiting the Notch1-HIF-1α/NF-κB signalling pathway. Frontiers in Immunology, 13, 816952. View Publication