Antimicrobial Peptide CATH-2 Attenuates Avian Pathogenic E. coli-Induced Inflammatory Response via NF-κB/NLRP3/MAPK...

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Cathelicidins possess anti-inflammatory properties.
• Chicken cathelicidin-2 (CATH-2) modulates immune responses, but its anti-inflammatory mechanisms remain unclear.
• Avian pathogenic E. coli (APEC) infection triggers inflammatory responses in host cells.

Purpose of the Study:

• To investigate the anti-inflammatory activity of CATH-2 on murine peritoneal macrophages during APEC infection.
• To elucidate the underlying molecular mechanisms of CATH-2's anti-inflammatory effects.
• To determine the role of lysosomal function and specific signaling pathways in CATH-2's action.

Main Methods:

• Murine peritoneal macrophages were primed with CATH-2 and subsequently infected with APEC.
• Cytokine production (IL-1β, IL-6, IL-1α, IL-12) was measured.
• Caspase-1 activation, NLRP3 inflammasome assembly, NF-κB and MAPK signaling pathways were assessed.
• Lysosomal function, including cathepsin B expression and acidification, was evaluated.
• The effect of ML-SA1 on lysosomal acidification and CATH-2's anti-inflammatory activity was examined.

Main Results:

• CATH-2 priming significantly reduced the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-1α, IL-12).
• CATH-2 attenuated APEC-induced caspase-1 activation and NLRP3 inflammasome assembly.
• CATH-2 inhibited the activation of NF-κB and MAPK signaling pathways.
• CATH-2 disrupted lysosomal function by inhibiting cathepsin B mRNA expression and lysosomal acidification.
• Enhancing lysosomal acidification with ML-SA1 diminished CATH-2's anti-inflammatory effect.

Conclusions:

• CATH-2 exhibits significant anti-inflammatory activity against APEC infection in macrophages.
• CATH-2 inhibits inflammation by targeting the NF-κB/NLRP3/MAPK pathway.
• CATH-2 exerts its anti-inflammatory effects, in part, through the disruption of lysosomal function.