Secretory leucocyte protease inhibitor regulates bone metabolism and inflammation in experimental mouse periodontitis

Abstract Secretory leukocyte protease inhibitor (SLPI), mainly secreted by epithelial cells, is abundant in saliva and other mucus secretions. In healthy periodontal tissues, SLPI maintains homeostasis by modulating immune responses and inhibiting tissue destruction through its neutrophil elastase activity. Recently, decreased SLPI levels have been found in severe periodontitis when compared to healthy individuals. In this study, we hypothesized that intragingival administration of SLPI would inhibit periodontal tissue destruction caused by periodontitis. SLPI administration significantly reduced neutrophil elastase activity in periodontal tissue and alleviated alveolar bone loss in mice. Real-time PCR analysis revealed that SLPI administration downregulated the transcription of proinflammatory cytokines and osteoclast-related factors in gingival tissue. In vitro, treatment of bone marrow macrophages with SLPI resulted in the downregulation of osteoclast differentiation. SLPI also inhibited osteoclast differentiation and promoted osteoblast mineralization in vitro. These findings suggest that SLPI prevents periodontal tissue destruction by affecting inflammation and bone metabolism.