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The Correlation Between IFNG Gene Methylation and Th1|Th2 Cell Balance in ROU and the Interventional Study of Jiaweidaochi Powder

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Abstract

The pathogenesis of recurrent oral ulcers (ROU) is complex, with a long duration of illness and challenging to cure. According to traditional Chinese medicine (TCM),”heat accumulation in the heart-spleen” is one of the main causative factors. Jiaweidaochi powder (JWDCP) is based on the ancient Chinese medicine formula JWDCS, with the addition of Tongcao and gypsum and the removal of Mu Tong. It is generally used to treat “heat accumulation in the heart-spleen.” Previous studies have demonstrated that it effectively reduces recurrence rates and is anti-inflammatory in modulating immunity. The ROU rats’ model for JWDCP intervention treatment had been established, and histological tests revealed that JWDCP has a therapeutic effect on the pathological changes in the oral mucosa. In addition, the methylation levels of peripheral blood IFNG gene were detected by bisulfite sequencing PCR (BSP), and the methylation levels of the IFNG promoter region in the model group and each dose group were lower than those in the control group. However, no significant methylation differences were observed. Furthermore, the results of enzyme-linked immunosorbent assay (ELISA) and RNA quantitative polymerase chain reaction showed that JWDCP could reduce IFN-γ and IL-4 protein concentrations, with high GATA-3 mRNA production, T-bet mRNAproduction was upgraded, elevated IL-4 mRNA levels, and reduced IFN-γ mRNA levels after treatment (P < 0.001). The expression of transcription factor T-betmRNA and GATA-3 gene mRNA was accompanied by changes in IFN-γmRNA and IL-4mRNA, demonstrating that Th2 type differentiation in RAS suppresses the body’s immunity and that the imbalance of transcription factor expression further leads to Th1/Th2 drift. JWDCP is likely to reduce the protein concentration by regulating the imbalance of transcription factors and enhancing antioxidant capacity, thus achieving therapeutic effects. Treatment of recurrent oral ulcer models is not sufficient to reset IFNG methylation levels, correlating with the refractoriness of ROU, further confirming the complexity of epigenetic mechanisms and that epigenetic alterations in specific mediators may persist locally.

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Funding

This work was supported by General Project of Shanxi Province Key R&D Program (No.201603D321044) and Postgraduate Innovation and Entrepreneurship Program of Shanxi University of Traditional Chinese Medicine (No.2021CX042).

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Authors and Affiliations

  1. Department of Graduate School, Shanxi University of Chinese Medicine, Taiyuan, 030619, China

    Yue Hu & Jiankun Weng

  2. Department of Traditional Chinese Medicine, First Hospital of Shanxi Medical University, Taiyuan, 030001, China

    Hongbo Guo

  3. Department of Traditional Chinese Medicine, Xingyi People’s Hospital, Xingyi, 562400, China

    Lu He

  4. Department of Graduate School, Shanxi Medical University, Taiyuan, 030001, China

    Qianqian Wang, Yanqing Li & Rong Zhang

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  1. Yue Hu
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The authors contributed equally.

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Correspondence to Hongbo Guo.

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Hu, Y., Guo, H., He, L. et al. The Correlation Between IFNG Gene Methylation and Th1|Th2 Cell Balance in ROU and the Interventional Study of Jiaweidaochi Powder. Appl Biochem Biotechnol 195, 6737–6751 (2023). https://doi.org/10.1007/s12010-023-04417-w

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