NLRP6 suppresses the inflammatory response of human periodontal ligament cells by inhibiting NF‐κB and ERK signal pathways

Abstract

Aim

To explore the function and mechanisms of NLRP6 (NOD‐, LRR‐ and pyrin domain‐containing 6) in the inflammatory response of human periodontal ligament cells (HPDLCs).

Methodology

Apical periodontitis tissues were obtained from 3 patients who received endodontic microsurgery. The expression of NLRP6 in 3 human apical periodontitis tissues and HPDLCs was examined by immunohistochemistry and immunofluorescence, respectively. The expressions of NLRP6, Phospho(p)‐ p65, p65, IκB‐α, p‐ IκB‐α, ERK, p‐ ERK, NLRP3, Pro interleukin (IL)‐1β, Pro caspase‐1 and apoptosis‐associated speck‐like protein containing a CARD (ASC) were examined by western blot. The gene expression and secretion of proinflammatory cytokines were detected by using quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Data were analysed statistically with independent sample t‐tests.

Results

NLRP6 was expressed in inflammatory periapical tissues and HPDLCs. Lipopolysaccharide (LPS) from Escherichia coli induced NLRP6 in HPDLCs (P<0.05). After silencing NLRP6, E. coli LPS‐induced activation of NF‐κB and ERK signaling was enhanced, which was also accompanied by elevated levels of IL‐6 and tumor necrosis factor‐α (TNF‐α) (P<0.05). Moreover, knockdown of NLRP6 led to up‐regulation of NLRP3, Pro IL‐1β and Pro caspase‐1 (P<0.05), whereas down‐regulation of ASC (P<0.05), which may contribute to unchanged levels of IL‐1β in HPDLCs inflammation.

Conclusion

NLRP6 was functionally expressed in inflammatory periapical tissues and HPDLCs. NLRP6 negatively regulated the production of IL‐6 and TNF‐α in HPDLCs inflammation by inhibiting NF‐κB and ERK signal pathways.

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