Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis.
OBJECTIVE
DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP).


METHODS
DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay.


RESULTS
The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03).


CONCLUSIONS
The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients.
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan; General Dentistry and Clinical Education Unit, Niigata University Medical and Dental Hospital, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan. Electronic address: kotetsuo@dent.niigata-u.ac.jp.
Tetsuo
T
Kobayashi
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
Kohei
K
Ishida
Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
Hiromasa
H
Yoshie
D000368:Aged; D001483:Base Sequence; D055113:Chronic Periodontitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005881:Gingiva / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017622:Periodontal Attachment Loss; D010512:Periodontal Index; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D016207:Cytokines; D015226:Dinucleoside Phosphates; D015850:Interleukin-6; D012333:RNA, Messenger; C508600:IL6 protein, human; C015772:CpG dinucleotide
Chronic periodontitis; DNA methylation; Gene expression; Interleukin-6