LincRNA‐EPS inhibits caspase‐11 and NLRP3 inflammasomes in gingival fibroblasts to alleviate periodontal inflammation

Abstract

AbstractTo investigate the effects of long intergenic noncoding RNA‐erythroid prosurvival (lincRNA‐EPS) on periodontal inflammation mediated by inflammasomes and to explore its mechanism. Experimental periodontitis was induced in KO (lincRNA‐EPS−/−) and WT (lincRNA‐EPS+/+) mice to compare the periodontal bone loss and inflammation by using micro‐computed tomography, immunofluorescence staining and haematoxylin and eosin staining. The expression and activation of cysteinyl aspartate‐specific proteinase‐11 (caspase‐11) and NOD‐like receptor protein 3 (NLRP3) inflammasomes, as well as nuclear factor‐kappa B (NF‐κB) activation in mouse gingival fibroblasts (MGFs), were measured by real‐time quantitative polymerase chain reaction, Western blotting, enzyme‐linked immunosorbent and lactate dehydrogenase assays. MGFs were transfected with overexpression plasmids to assess the biological functions of lincRNA‐EPS. RNA pull‐down and immunoprecipitation experiments were performed to identify the interacting protein of lincRNA‐EPS. LincRNA‐EPS‐expressing lentivirus was locally administered to inflamed periodontal tissues to evaluate its salvage function in periodontitis. The absence of lincRNA‐EPS increased bone loss and expression of myeloperoxidase, interleukin‐1α (IL‐1α) and IL‐1β in the inflammatory periodontium. LincRNA‐EPS KO MGFs exhibited increased expression and activation of caspase‐11/NLRP3 inflammasome components than WT MGFs under lipopolysaccharide (LPS) stimulation. The expression and activation of these molecules were inhibited in lincRNA‐EPS overexpressed MGFs. Mechanistically, lincRNA‐EPS directly bound to transactive response DNA‐binding protein 43 (TDP43) in the nucleus of MGFs, and TDP43 knockdown exerted a similar inhibitory effect on NF‐κB activation and the inflammasomes as lincRNA‐EPS overexpression. Locally injecting lincRNA‐EPS‐expressing lentivirus weakened the periodontal damage. LincRNA‐EPS inhibits the LPS‐induced production and activation of caspase‐11 and NLRP3 inflammasomes by suppressing the activation of the NF‐κB signalling pathway via interacting with TDP43, thereby alleviating periodontitis.