Calcitriol Suppressed Inflammatory Reactions in IL-1β-Stimulated Human Periodontal Ligament Cells

Abstract

Vitamin D has important roles on control of calcium and phosphate levels in the body. However, the role of vitamin D on the pathogenesis of periodontal disease is still uncertain. Therefore, we examined the effect of the hormonal form of vitamin D, calcitriol, on inflammatory responses of human periodontal ligament cells (HPDLC). We detected vitamin D receptor expression in non-stimulated HPDLC. Calcitriol inhibited interleukin (IL)-6, IL-8, CC chemokine ligand (CCL) 20, CXC chemokine ligand (CXCL) 10, and matrix metalloproteinase (MMP)-3 release from IL-1β-stimulated HPDLC. Tissue inhibitor of metalloproteinase (TIMP)-1 production did not change by calcitriol. Moreover, we found c-jun N-terminal kinase (JNK) phosphorylation and IκB-α degradation in IL-1β-stimulated HPDLC were inhibited by calcitriol, and JNK and nuclear factor (NF)-κB inhibitors could decrease IL-6, IL-8, CCL20, CXCL10, and MMP-3 productions in IL-1β-treated HPDLC. These findings suggest that vitamin D could modulate inflammatory response in periodontal tissues.

Calcitriol suppresses lipopolysaccharide‐induced alveolar bone damage in rats by regulating T helper cell subset polarization

“…Our data demonstrated that continuous local LPS injection into the gingival sulcus, which is a common method for generating experimental periodontitis in rats for research purposes, could induce local inflammatory responses, bone damage, and finally periodontitis . During the development of periodontitis, systemic calcitriol administration via oral gavage was used to influence bone resorption because substantial evidence indicates that calcitriol can act as a therapeutic agent for periodontal disease . Based on micro‐CT analysis, we found that rats that underwent LPS injection while simultaneously receiving calcitriol intervention (LPS + Cal group) exhibited decreased bone resorption compared with those without calcitriol intervention (LPS group).…”

“…33 During the development of periodontitis, systemic calcitriol administration via oral gavage was used to influence bone resorption because substantial evidence indicates that calcitriol can act as a therapeutic agent for periodontal disease. 13,[21][22][23] Based on micro-CT analysis, we found that rats that underwent LPS injection while simultaneously receiving calcitriol intervention (LPS + Cal group) exhibited decreased bone resorption compared with those without calcitriol intervention (LPS group). When bone destruction was analyzed by micro-CT-reconstructed 3D models, the LPS + Cal group showed in a higher BV/TV ratio than the LPS group.…”

“…Although the changes in cytokine levels may also result in the polarization of other immune cells, such as macrophages, the capacity of calcitriol to inhibit proinflammatory cytokines and stimulate anti‐inflammatory cytokine release during periodontitis underscores its therapeutic function. Calcitriol has also been confirmed to induce the downregulation of proinflammatory cytokines, including IL‐1β, IL‐6 and IL‐8, in inflammatory reactions; these molecules have the same role in osteoclastogenesis as in inflammatory reactions . However, calcitriol plays a significant role in the development of regulatory T cells that produce cytotoxic T lymphocyte‐associated protein 4 (CTLA‐4) and forkhead/winged helix transcription factor p3 (FoxP3), which may induce valid immune suppression and trigger increased IL‐10 levels and Treg cell proliferation …”

“…Calcitriol has also been confirmed to induce the downregulation of proinflammatory cytokines, including IL-1β, IL-6 and IL-8, in inflammatory reactions; these molecules have the same role in osteoclastogenesis as in inflammatory reactions. 21 However, calcitriol plays a significant role in the development of regulatory T cells that produce cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and forkhead/ winged helix transcription factor p3 (FoxP3), which may induce valid immune suppression and trigger increased IL-10 levels and Treg cell proliferation. 51,52 The levels of various cytokines in the DRs underscore a trend of Th cell polarization toward a particular subset but do not directly reflect accurate cell polarization counts.…”

Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children

“…Moreover, we found increased expression of TNF-a, a gene stimulated by IL-33 [29], and IL-1B, a gene involved in the activation of IL-33 [30]. Finally, we found that RV induced genes that are targets of 25(OH)-VitD3, such as Gene arrays of RNA from in-vitro rhinovirus (RV)-infected peripheral blood mononuclear cells (PBMCs) of preschool children with asthma revealed the induction of innate lymphoid cell type 2 (ILC2)-associated genes.…”