Highly Soluble Mussel Foot Protein and Its Derivatives Inhibit Inflammation by Targeting NF-κB/PI3K-Akt Signaling and...

Area of Science:

• Biomaterials Science
• Immunology
• Pharmacology

Background:

• Chronic inflammation is linked to numerous diseases, necessitating novel anti-inflammatory agents.
• Mussel foot proteins are explored for their biocompatibility and diverse biological activities.
• Natural compounds offer potential as safe and effective anti-inflammatory therapies.

Purpose of the Study:

• To evaluate the anti-inflammatory potential of highly soluble mussel foot protein (HMFP) and HMFP-PEG.
• To investigate the underlying molecular mechanisms of HMFP and HMFP-PEG in an in vitro inflammation model.
• To assess the impact on inflammatory mediators, signaling pathways, and macrophage polarization.

Main Methods:

• Utilized LPS-stimulated RAW264.7 cells as an in vitro inflammation model.
• Assessed intracellular reactive oxygen species (ROS) levels and pro-inflammatory cytokine secretion (IL-1β, TNF-α, NO).
• Analyzed the phosphorylation of key signaling molecules (PI3K, Akt, NF-κB, IκB) and macrophage polarization markers (iNOS, CD206).

Main Results:

• Both HMFP and HMFP-PEG significantly reduced ROS and suppressed pro-inflammatory mediators while increasing anti-inflammatory cytokines (IL-10, TGF-β).
• These agents inhibited LPS-induced phosphorylation of PI3K/Akt and NF-κB signaling pathways.
• HMFP and HMFP-PEG downregulated iNOS expression and upregulated CD206, promoting M2 macrophage polarization.

Conclusions:

• HMFP and HMFP-PEG exhibit potent anti-inflammatory effects by dual inhibition of NF-κB and PI3K/Akt signaling.
• These compounds promote macrophage polarization towards an anti-inflammatory M2 phenotype.
• HMFP and HMFP-PEG demonstrate significant potential as therapeutic candidates for inflammation-related diseases.