Effect of 1,25(OH)2D3 and 20(OH)D3 on interleukin-1β-stimulated interleukin-6 and -8 production by human gingival fibroblasts

V. Nakashyan, David Tipton, Anastasios Karydis, R. Livada, Sidney Stein

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7 Citations (Scopus)

Abstract

Background and Objective: Vitamin D—1,25(OH)2D3 or 1,25D3—maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3—20(OH)D3 or 20D3—on IL-1β-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. Material and Methods: Human gingival fibroblasts were incubated ± IL-1β, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. Results: IL-1β-stimulated IL-6 and IL-8 levels were both significantly inhibited (40%-60%) (P<.045) by 1,25D3, but not 20D3 (0%-15% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1β-stimulated nuclear levels of p65 and phospho-cJun (P<.02). Conclusion: Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1β stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.

Original languageEnglish (US)
Pages (from-to)832-841
Number of pages10
JournalJournal of Periodontal Research
Volume52
Issue number5
DOIs
StatePublished - Oct 1 2017

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Interleukin-8
Interleukin-1
Transcription Factor AP-1
Interleukin-6
Fibroblasts
Periodontitis
Gene Expression
Calcitriol Receptors
Chemotactic Factors
Hypercalcemia
Bone Resorption
Vitamins
Oligonucleotides
Analysis of Variance
Neutrophils
Anti-Inflammatory Agents
Enzyme-Linked Immunosorbent Assay
20-hydroxyvitamin D3
Ligands
Inflammation

All Science Journal Classification (ASJC) codes

  • Periodontics

Cite this

@article{4790801a07b6401193b7233772083f59,
title = "Effect of 1,25(OH)2D3 and 20(OH)D3 on interleukin-1β-stimulated interleukin-6 and -8 production by human gingival fibroblasts",
abstract = "Background and Objective: Vitamin D—1,25(OH)2D3 or 1,25D3—maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3—20(OH)D3 or 20D3—on IL-1β-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. Material and Methods: Human gingival fibroblasts were incubated ± IL-1β, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. Results: IL-1β-stimulated IL-6 and IL-8 levels were both significantly inhibited (40{\%}-60{\%}) (P<.045) by 1,25D3, but not 20D3 (0{\%}-15{\%} inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1β-stimulated nuclear levels of p65 and phospho-cJun (P<.02). Conclusion: Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1β stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.",
author = "V. Nakashyan and David Tipton and Anastasios Karydis and R. Livada and Sidney Stein",
year = "2017",
month = "10",
day = "1",
doi = "10.1111/jre.12452",
language = "English (US)",
volume = "52",
pages = "832--841",
journal = "Journal of Periodontal Research",
issn = "0022-3484",
publisher = "Blackwell Munksgaard",
number = "5",

}

TY - JOUR

T1 - Effect of 1,25(OH)2D3 and 20(OH)D3 on interleukin-1β-stimulated interleukin-6 and -8 production by human gingival fibroblasts

AU - Nakashyan, V.

AU - Tipton, David

AU - Karydis, Anastasios

AU - Livada, R.

AU - Stein, Sidney

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background and Objective: Vitamin D—1,25(OH)2D3 or 1,25D3—maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3—20(OH)D3 or 20D3—on IL-1β-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. Material and Methods: Human gingival fibroblasts were incubated ± IL-1β, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. Results: IL-1β-stimulated IL-6 and IL-8 levels were both significantly inhibited (40%-60%) (P<.045) by 1,25D3, but not 20D3 (0%-15% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1β-stimulated nuclear levels of p65 and phospho-cJun (P<.02). Conclusion: Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1β stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.

AB - Background and Objective: Vitamin D—1,25(OH)2D3 or 1,25D3—maintains healthy osseous tissue, stimulates the production of the antimicrobial peptide cathelicidin and has anti-inflammatory effects, but it can cause hypercalcemia. Evidence links diminished serum levels of 1,25D3 with increased gingival inflammation. Periodontitis progression is associated with increased local production of inflammatory mediators by immune cells and gingival fibroblasts. These include interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8, both regulated by signaling pathways, including NF-κB and MAPK/AP-1. The objectives were to determine the effects of 1,25D3 or a non-calcemic analog, 20-hydroxyvitamin D3—20(OH)D3 or 20D3—on IL-1β-stimulated IL-6 and IL-8 production, and NF-κB and MAPK/AP-1 activation, by human gingival fibroblasts. Material and Methods: Human gingival fibroblasts were incubated ± IL-1β, with or without exposure to 1,25D3 or 20D3. IL-6 and IL-8 in culture supernatants were measured by enzyme-linked immunosorbent assay. NF-κB (p65) and AP-1 (phospho-cJun) and were measured in nuclear extracts via binding to specific oligonucleotides. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. Results: IL-1β-stimulated IL-6 and IL-8 levels were both significantly inhibited (40%-60%) (P<.045) by 1,25D3, but not 20D3 (0%-15% inhibition, not statistically significant). Both 1,25D3 and 20D3 significantly and similarly inhibited IL-1β-stimulated nuclear levels of p65 and phospho-cJun (P<.02). Conclusion: Reduction of the activation of NF-κB and AP-1 alone is not able to inhibit strongly the IL-1β stimulated IL-6 and IL-8 gene expression. 1,25D3 but not 20D3 may affect some of the many other factors/processes/pathways that in turn regulate the expression of these genes. However, the results suggest that topical application of ligands of the vitamin D receptor may be useful in the local treatment of periodontitis while reducing adverse systemic effects.

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U2 - 10.1111/jre.12452

DO - 10.1111/jre.12452

M3 - Article

VL - 52

SP - 832

EP - 841

JO - Journal of Periodontal Research

JF - Journal of Periodontal Research

SN - 0022-3484

IS - 5

ER -