Slpi, known as Secretory Leukocyte Protease Inhibitor, is a pleiotropic protein mainly expressed by epithelial cells at mucosal surfaces [1]. It inhibits proteases, exerts antimicrobial activity, and inhibits NF-κB-mediated inflammatory gene transcription, thus maintaining homeostasis at barrier tissues, protecting against inflammation, and regulating the threshold of inflammatory immune responses [1].

In a mouse model, genetic ablation of Slpi severely impairs PTH-induced bone formation [2]. Slpi induction in osteoblasts enhances its differentiation and suppresses osteoclastic function, demonstrating that Slpi regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism [2]. In another model, crossing ENaC-Tg mice with SLPI knock-out (SLPI-/-) mice showed that SLPI deficiency alters airway protease activity and induces cell recruitment in a model of muco-obstructive lung disease, suggesting a role of decreased SLPI levels in the pathogenesis of such diseases [3].

In conclusion, Slpi is crucial for maintaining tissue homeostasis, with its functions ranging from protecting against inflammation to promoting bone anabolism. Gene knockout mouse models have revealed its role in bone formation and muco-obstructive lung disease, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Nugteren, Sandrine, Samsom, Janneke N. 2021. Secretory Leukocyte Protease Inhibitor (SLPI) in mucosal tissues: Protects against inflammation, but promotes cancer. In Cytokine & growth factor reviews, 59, 22-35. doi:10.1016/j.cytogfr.2021.01.005. https://pubmed.ncbi.nlm.nih.gov/33602652/

2. Morimoto, Akito, Kikuta, Junichi, Nishikawa, Keizo, Matsuda, Hideo, Ishii, Masaru. 2021. SLPI is a critical mediator that controls PTH-induced bone formation. In Nature communications, 12, 2136. doi:10.1038/s41467-021-22402-x. https://pubmed.ncbi.nlm.nih.gov/33837198/

3. Brown, Ryan, Dougan, Caoifa, Ferris, Peter, Weldon, Sinéad, Taggart, Clifford C. 2024. SLPI deficiency alters airway protease activity and induces cell recruitment in a model of muco-obstructive lung disease. In Frontiers in immunology, 15, 1433642. doi:10.3389/fimmu.2024.1433642. https://pubmed.ncbi.nlm.nih.gov/39301022/