NLRP3 Mediates Submandibular Gland Regeneration in Duct Ligation/De-Ligation Model.

Abstract

OBJECTIVE: The initial inflammatory response following tissue injury activates macrophages, which are essential for tissue regeneration. NLRP3 plays a crucial role in initiating this inflammatory response and is involved in tissue regenerative repair. However, the relationship between inflammation and regeneration during salivary regeneration is uncertain. The purpose of this study is to investigate the function of NLRP3 interaction with macrophage-mediated submandibular gland regeneration. MATERIALS AND METHODS: The rat model of submandibular gland duct ligation/de-ligation was established to assess NLRP3 activation during both the injury and regeneration phases. A specific NLRP3 knockdown model was developed using a retrograde transduction method in the submandibular gland to investigate the relationship between NLRP3 and salivary gland regeneration. In vitro CCL2 induction of THP-1 cells and in vivo salivary gland transduction of CCL2 validate the relationship between CCL2 and macrophages. RESULTS: NLRP3 was activated during the ligation and de-ligation of the rat submandibular gland. NLRP3 knockdown inhibited submandibular gland regeneration, reduced the release of inflammatory and chemokine factors, inhibited macrophage recruitment, and affected macrophage polarization. When NLRP3 signaling was inhibited, CCL2 supplementation restored compromised macrophage activation and cell proliferation. CONCLUSION: NLRP3 modulates macrophage activation through CCL2 regulation, promoting submandibular gland tissue regeneration.