母獣のフルクトース過剰摂取はBDNFプロモーター領域のDNA高メチル化を介して、仔の海馬機能の低下を引き起こす

藤田医科大

Differences in Cytokine Gene Expression after a Stimulation with Escherichia Coli and Porphyromonas Gingivalis or Lipopolysaccharides Derived from these Bacteria

Monocytes are important cells in innate immunity. The early stage of the innate immunity is regulated by various cytokines produced by monocytes. We conducted a preliminary study to investigate TNFα expression by stimulating THP-1 cells with several bacterial species. The TNFα mRNA levels significantly varied, with the most potent stimulatory effects observed with P. gingivalis. In the present study, we focused on P. gingivalis and compared differences in cytokine expression profiles after the stimulation of THP-1 with E. coli. Bacterial antigen stimulation increased various cytokine gene expressions in THP-1. P. gingivalis had significantly more potent effects on the mRNA expressions of TNFα, IL-1β, and IL-10, but not of IL-12p40, than E. coli. This result suggests the potent ability of P. gingivalis to induce inflammation. THP-1 stimulated with LPS derived from both bacterial species showed that E. coli had significantly more potent effects on the expressions of TNFα, IL-1β, and IL-12p40 than P. gingivalis. The differences in the bacterial antigens and the LPS stimulation effects suggest involvements of different receptors, such as TLR-2 and -4, which recognize bacterial components. The present results suggest that the P. gingivalis somatic cell antigen stimulates a number of pattern recognition receptors at the same time as the synthesis of bacterial components, except LPS. The potent virulence of P. gingivalis and persistence of infection might be affected by differences in cytokine production. Pro-inflammatory responses are dependent not only on the bacterial type, but also bacterial components

Association of smoking habits with TXNIP DNA methylation levels in leukocytes among general Japanese population.

Thioredoxin-interacting protein (TXNIP) inhibits the activity of thioredoxin (TXN), leading to increased oxidative stress. Expression of the TXNIP gene is regulated by DNA methylation. However, no study has reported the influence of lifestyle factors on TXNIP DNA methylation. Our goal was to determine the association between smoking habits and TXNIP DNA methylation levels in a Japanese population. We conducted a cross-sectional study of 417 subjects (180 males and 237 females) participating in a health examination. We used a pyrosequencing assay to determine TXNIP DNA methylation levels in leukocytes. The mean TXNIP DNA methylation level in current smokers (75.3%) was significantly lower than that in never and ex-smokers (never: 78.1%, p < 0.001; ex: 76.9%, p = 0.013). Multivariable logistic regression analyses showed that the OR for TXNIP DNA hypomethylation was significantly higher in current smokers than that in never smokers, and significantly higher in current smokers with years of smoking ≥ 35 and Brinkman Index ≥ 600 compared to that in non-smokers. In conclusion, we found that current smokers had TXNIP DNA hypomethylation compared to never and ex-smokers. Moreover, long-term smoking and high smoking exposure also were associated with TXNIP DNA hypomethylation