Upregulated Leptin in Periodontitis Promotes Inflammatory Cytokine Expression in Periodontal Ligament Cells

Imbalance or disruption in the expression of inflammatory mediators contributes greatly to the breakdown of the periodontal supporting tissues. Leptin, through binding to its receptor (obesity-related leptin and leptin receptor [OBR]), has potent effects on immunity and inflammation. However, to date, researchers only indicated a role of leptin in periodontitis. No direct or valid evidence exists about how leptin and its receptor are regulated by local inflammation, what effects they have, and the underlying mechanisms.

Experimental periodontitis was induced by ligation of mandibular second molars in beagle dogs. The expression of leptin, OBR, and interleukin (IL)-1β was examined by immunohistochemistry. Meanwhile, recombinant human IL-1β was used to stimulate human periodontal ligament cells (hPDLCs) in vitro, and mRNA and protein levels of leptin were measured using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Then, mRNA and protein levels of IL-6 and IL-8 were measured using real-time PCR and ELISA, after stimulation with various concentrations of leptin, knocking down all or only the long form of OBR (OBRb) by small interfering RNA and incubation with multiple intracellular signaling pathway inhibitors, respectively.

Leptin and OBR increased substantially in inflammatory periodontal tissues, which correlated well with the extent of inflammatory infiltration, and was a result of the upregulation in resident cells themselves. A high dose of leptin could induce the expression of mRNA and protein of IL-6 and IL-8 in hPDLCs through binding with OBRb and activating different intracellular signaling pathways.

Upregulated leptin and OBR in periodontitis stimulated proinflammatory cytokine expression in PDL cells to additionally promote local inflammation.