Antimicrobial and immune-modulating effects of recombinant pancreatitis-associated protein in the treatment of MRSA-induced severe septic arthritis.

Septic arthritis is a severe infection caused by bacteria directly invading the synovial joints. It leads to inflammatory damage to articular cartilage and may result in significant functional impairment, with a high recurrence rate. The rapid spread of antibiotic-resistant bacterial strains has further exacerbated the threat to human health, particularly in septic arthritis cases. Based on the antibacterial activity and regenerative properties of pancreatitis-associated protein (PAP), the present study aims to investigate the therapeutic potential of exogenous recombinant PAP for treating methicillin-resistant Staphylococcus aureus (MRSA)-induced septic arthritis. The prepared PAP exhibited favorable bactericidal effects against both Staphylococcus aureus (S. aureus) and MRSA in a dose-dependent manner. The antibacterial efficacy in the high-dose group was comparable to that of vancomycin. Additionally, 10 nM PAP significantly promoted the proliferation of RAW264.7 macrophages and enhanced their resistance to oxidative stress. Intra-articular injection of PAP accelerated the recovery from MRSA-induced septic arthritis by alleviating joint swelling, clearing the bacteria within the joint cavity, and mitigating inflammation. Transcriptomic results indicated that PAP administration significantly down-regulated the expression of inflammatory markers and slightly increased the proportion of monocytes/macrophages. Further studies on the immunomodulatory effects of PAP revealed that it attenuated lipopolysaccharide (LPS)-induced M1 polarization and markedly diminished the expression of pro-inflammatory cytokines, including TNF-α, IFN-γ, and IL-6. Meanwhile, PAP partially induced M2 polarization of macrophages and elevated anti-inflammatory IL-4 levels. In conclusion, PAP exhibited antibacterial, tissue repair, and immunomodulatory activities, highlighting its potential as a therapeutic candidate for septic arthritis.