Cytokine gene expression profiles during initiation, progression and resolution of periodontitis

J Clin Periodontol. 2014 Sep;41(9):853-61. doi: 10.1111/jcpe.12286. Epub 2014 Jul 24.

Abstract

Aim: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs).

Materials and methods: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus Gene 1.0 ST (Affymetrix) used for gene expression analysis. Significant expression changes were validated by qRT-PCR.

Results: Disease initiation/progression was characterized by overexpression of Th17/Treg cytokine genes (IL-1β, IL-6, TGFβ and IL-21) and down-regulation of Th1/Th2 cytokine genes (IL-18 and IL-25). Increased IL-2 and decreased IL-10 levels were seen during disease resolution. Several Th17/Treg cytokine genes positively correlated with TDGs, whereas most Th1/Th2 genes exhibited a negative correlation.

Conclusion: Initiation, progression and resolution of periodontitis involve over- and underexpression of cytokine genes related to various T-helper subsets. In addition, variations in individual T-helper response subset/genes during disease progression correlated with protective/destructive outcomes.

Keywords: RANKL; T-helper cytokines; adaptive immunity; gingival tissue; matrix metalloproteinase; periodontitis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cathepsin K / genetics
  • Cytokines / genetics*
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Profiling*
  • Interleukin-10 / genetics
  • Interleukin-17 / genetics
  • Interleukin-18 / genetics
  • Interleukin-1beta / genetics
  • Interleukin-2 / genetics
  • Interleukin-6 / genetics
  • Interleukins / genetics
  • Macaca mulatta
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Periodontitis / genetics
  • Periodontitis / immunology*
  • Periodontitis / physiopathology
  • RANK Ligand / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Transforming Growth Factor beta / genetics

Substances

  • Cytokines
  • Interleukin-17
  • Interleukin-18
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Interleukins
  • RANK Ligand
  • Transforming Growth Factor beta
  • Interleukin-10
  • Cathepsin K
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • interleukin-21