Impact of nicotine on the interplay between human periodontal ligament cells and CD4⁺ T cells

Abstract

<jats:p> Periodontitis is a common infectious disease associated with destruction of periodontal ligaments and alveolar bones. CD4<jats:sup>+</jats:sup> T cell-mediated immune response is involved in the progression of periodontitis. Tobacco consumption increases the risk of periodontal disease. However, the impact of nicotine on the interaction between human periodontal ligament (PDL) cells and CD4<jats:sup>+</jats:sup> T cells remains unrevealed. Our study aims to investigate the effect of nicotine on PDL cells and the cocultured CD4<jats:sup>+</jats:sup> T cells. The PDL cell cultures were established by explants from healthy individuals, exposed to nicotine or α-bungarotoxin (α-BTX), and incubated solely or in combination with CD4<jats:sup>+</jats:sup> T cells. Afterwards, cell viability, secreted cytokines, and matrix metalloproteinases (MMPs) were evaluated. In monoculture of PDL cells, nicotine dramatically repressed cell viability and increased apoptosis. Meanwhile, α-BTX largely reversed the nicotine-induced apoptosis and increased viability of PDL cells. Compared with the monoculture, MMP-1, MMP-3, interleukin (IL)-1β, IL-6, IL-17, and IL-21 in supernatant of cocultures were markedly elevated after treatment with nicotine. Moreover, α-BTX significantly attenuated nicotine-triggered production of these components either in mono- or co-cultures. In addition, PDL cell-derived CXCL12 following nicotine treatment recruited CD4<jats:sup>+</jats:sup> T cells. Above all, nicotine deteriorated periodontitis partially by promoting PDL cell–CD4<jats:sup>+</jats:sup> T cell-mediated inflammatory response and matrix degradation. </jats:p>

Effect of tobacco on periodontal disease and oral cancer

“…In human studies, T cells infiltrating gingival lesions expressed mRNA for T-helper (Th)1/Th2 and for regulatory cytokines 58 . Nicotine deteriorates periodontal disease partially by promoting PDL cell–CD4+T cell-mediated inflammatory response and matrix degradation 59 . On the other hand, P. gingivalis LPS-stimulated monocyte-derived dendritic cells induced increased proliferation with increasing dendritic cells (DC) number.…”

Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects

“…When human periodontal ligament cells were cocultured with CD4 + T cells, nicotine (10 -5 M, 24 h) dramatically repressed cell viability and increased apoptosis, which was associated with the collapse of periodontal tissues and elevated matrix metalloproteinases MMP1, MMP3, and cytokines IL-1b, IL-6, IL-17, IL-21, and chemokines CXCL12. The receptor a7 nAChR played a major mediating role, and its inhibitor a-bungarotoxin reversed nicotineinduced apoptosis, increased viability, and attenuated the nicotinetriggered production of these factors (80). In addition to inflammatory cytokines and osteoclast markers, other molecules may also participate in nicotine-induced periodontitis.…”

Nicotine regulates autophagy of human periodontal ligament cells through α7 nAchR that promotes secretion of inflammatory factors IL-1β and IL-8

“…Cell culture supernatants were analyzed using ELISA for detecting IL-1β and IL-8 release as described previously [ 26 ]. The highly sensitive ELISA kits from R&D systems (Minneapolis) were used to analyze IL-1β and IL-8 concentrations and normalized to the number of cells.…”