Boswellic acids target the human immune system-modulating antimicrobial peptide LL-37

Area of Science:

• Immunology
• Pharmacology
• Natural Products Chemistry

Background:

• The human cathelicidin LL-37 peptide modulates the immune system and is implicated in autoimmune diseases.
• Boswellic acids (BAs), derived from frankincense, are known for anti-inflammatory effects, but their precise molecular targets remain unclear.

Purpose of the Study:

• To identify functional targets of Boswellic acids (BAs).
• To investigate the interaction between BAs and the antimicrobial peptide LL-37.
• To explore the potential of BAs as modulators of LL-37 activity.

Main Methods:

• Unbiased target fishing using immobilized BAs and human neutrophils.
• MALDI-TOF mass spectrometry for identifying binding partners.
• Circular dichroism spectroscopy for confirming direct interaction and thermal stability.
• Cell-free limulus amoebocyte lysate assay to assess LL-37 functionality inhibition.

Main Results:

• Human LL-37 was identified as a direct binding partner of BAs.
• BAs, specifically 3-O-acetyl-β-BA (Aβ-BA) and 3-O-acetyl-11-keto-β-BA (AKβ-BA), inhibited LL-37's LPS-neutralizing activity.
• Inhibition was observed in cell-free assays, neutrophil supernatants, and human plasma.

Conclusions:

• Boswellic acids (BAs) are identified as direct inhibitors of the human antimicrobial peptide LL-37.
• This interaction may represent a key mechanism underlying the anti-inflammatory properties of BAs.
• BAs show potential as therapeutic agents or chemical tools for modulating LL-37-related disorders.