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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\u00a0nM 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-\u03b1, IFN-\u03b3, 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.<\/jats:p>","DOI":"10.1042\/cs20250060","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:23:12Z","timestamp":1778253792000},"page":"1059-1075","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimicrobial and immune-modulating effects of recombinant pancreatitis-associated protein in the treatment of MRSA-induced severe septic arthritis"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7859-211X","authenticated-orcid":false,"given":"Luting","family":"Yu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiangsu Provincial University Key Laboratory of Green Biomanufacturing for Pharmaceuticals, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghao","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiangsu Provincial University Key Laboratory of Green Biomanufacturing for Pharmaceuticals, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglong","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiangsu Provincial University Key Laboratory of Green Biomanufacturing for Pharmaceuticals, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiangsu Provincial University Key Laboratory of Green Biomanufacturing for Pharmaceuticals, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiangsu Provincial University Key Laboratory of Green Biomanufacturing for Pharmaceuticals, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jiangsu Provincial University Key Laboratory of Green Biomanufacturing for Pharmaceuticals, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"2026052512020395500_B1","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/S0140-6736(09)61595-6","article-title":"Bacterial septic arthritis in adults","volume":"375","author":"Mathews","year":"2010","journal-title":"Lancet"},{"key":"2026052512020395500_B2","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/s41579-022-00686-0","article-title":"Skeletal infections: microbial pathogenesis, immunity and clinical management","volume":"20","author":"Masters","year":"2022","journal-title":"Nat. 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