Chlojaponilactone B Attenuates THP-1 Macrophage Pyroptosis by Inhibiting the TLR/MyD88/NF-κB Pathway

Area of Science:

• Immunology
• Pharmacology
• Molecular Biology

Background:

• Pyroptosis is a crucial inflammatory response in innate immunity implicated in various diseases.
• Blocking pyroptosis is a therapeutic target, but effective drugs are lacking.
• Chojaponilactone B (CJB), a natural product, exhibits anti-inflammatory properties, but its effect on pyroptosis is unknown.

Purpose of the Study:

• To investigate the inhibitory effect of CJB on macrophage pyroptosis.
• To elucidate the underlying molecular mechanisms of CJB's anti-pyroptotic action.

Main Methods:

• Established an LPS/ATP-induced THP-1 macrophage pyroptosis model.
• Assessed pyroptosis markers including NLRP3, caspase 1, N-GSDMD, IL-1β, and IL-18.
• Utilized RNA sequencing to analyze gene expression changes.
• Investigated the TLR/MyD88/NF-κB signaling pathway and NF-κB p65 nuclear translocation.

Main Results:

• CJB significantly inhibited LPS/ATP-induced pyroptosis in THP-1 macrophages.
• CJB reduced the expression of NLRP3, caspase 1, N-GSDMD, IL-1β, and IL-18.
• RNA sequencing indicated CJB modulates inflammatory and anti-pyroptotic signaling pathways.
• CJB suppressed TLRs, MyD88, pro-IL-1β, and NF-κB activation, inhibiting NF-κB p65 nuclear translocation.

Conclusions:

• CJB effectively inhibits NLRP3 inflammasome activation and subsequent macrophage pyroptosis.
• The mechanism involves the suppression of the TLR/MyD88/NF-κB signaling pathway.
• CJB shows promise as a potential therapeutic agent for pyroptosis-related inflammatory diseases.