Slit guidance ligand 2 promotes the inflammatory response of periodontitis through activation of the NF-kappaB signaling pathway.

BACKGROUND AND OBJECTIVES: Periodontitis is a chronic multifactorial inflammatory disease associated with dental plaque biofilms. Slit guidance ligand 2 (SLIT2) has been shown to guide neuronal migration, regulate the inflammatory response and cancer progression. However, the role of SLIT2 in periodontitis is poorly understood. In this study, we investigated the expression of SLIT2 in the gingiva of periodontitis and its role in periodontitis progression. METHODS: Gingiva and gingival crevicular fluid (GCF) were collected from healthy people and periodontitis patients. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to analyze SLIT2 secretion level. Healthy human gingival fibroblasts (hGFs) were isolated and the expression of SLIT2 in lipopolysaccharide (LPS)-treated hGFs was detected. The effect of SLIT2 on inflammation was analyzed using western blot and immunofluorescence. SLIT2 knockdown (KD) and overexpression assays in hGFs were performed to investigate the role of SLIT2 in the LPS-induced inflammatory response. RESULTS: Gingival tissues and GCF of periodontitis patients displayed higher expression of SLIT2. Similarly, SLIT2 was upregulated in hGFs in an inflammatory environment (LPS treatment). In addition, SLIT2 treatment increased the expression of the inflammatory mediators interleukin-6 (IL-6) and IL-8 in hGFs. Mechanistically, SLIT2 stimulated the activation of nuclear factor-kappaB (NF-kappaB) signaling, as well as LPS. Lastly, SLIT2 KD impaired LPS-induced IL-6 production in hGFs, while SLIT2 overexpression amplified the inflammatory response. CONCLUSION: SLIT2 may be involved in the aggravation of periodontitis by activating NF-kappaB signaling in hGFs.