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

• Published in: Journal of clinical periodontology 2014-09, Vol.41 (9), p.853-861
• Main Authors: Ebersole, Jeffrey L., Kirakodu, Sreenatha, Novak, Michael John, Stromberg, Arny J., Shen, Shu, Orraca, Luis, Gonzalez-Martinez, Janis, Burgos, Armando, Gonzalez, Octavio A.
• Format: Article
• Language: English
• Subjects: adaptive immunity; Animals; Cathepsin K - genetics; Cytokines; Cytokines - genetics; Dentistry; Disease Models, Animal; Disease Progression; Female; Gene expression; Gene Expression Profiling; gingival tissue; Gum disease; 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; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 9 - genetics; periodontitis; Periodontitis - genetics; Periodontitis - immunology; Periodontitis - physiopathology; RANK Ligand - genetics; RANKL; T-helper cytokines; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Th2 Cells - immunology; Transforming Growth Factor beta - genetics
• ISSN: 0303-6979; 1600-051X
• DOI: 10.1111/jcpe.12286

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.