Frontiers in Immunology (Jul 2020)
Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway
- Luxi Cao,
- Luxi Cao,
- Luxi Cao,
- Luxi Cao,
- Luxi Cao,
- Tingting Zhu,
- Tingting Zhu,
- Tingting Zhu,
- Tingting Zhu,
- Tingting Zhu,
- Xiabing Lang,
- Xiabing Lang,
- Xiabing Lang,
- Xiabing Lang,
- Xiabing Lang,
- Sha Jia,
- Sha Jia,
- Sha Jia,
- Sha Jia,
- Sha Jia,
- Yi Yang,
- Yi Yang,
- Yi Yang,
- Yi Yang,
- Yi Yang,
- Chaohong Zhu,
- Chaohong Zhu,
- Chaohong Zhu,
- Chaohong Zhu,
- Chaohong Zhu,
- Yucheng Wang,
- Yucheng Wang,
- Yucheng Wang,
- Yucheng Wang,
- Yucheng Wang,
- Shi Feng,
- Shi Feng,
- Shi Feng,
- Shi Feng,
- Shi Feng,
- Cuili Wang,
- Cuili Wang,
- Cuili Wang,
- Cuili Wang,
- Cuili Wang,
- Ping Zhang,
- Ping Zhang,
- Ping Zhang,
- Ping Zhang,
- Ping Zhang,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang
Affiliations
- Luxi Cao
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Luxi Cao
- Key Laboratory of Nephropathy, Hangzhou, China
- Luxi Cao
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Luxi Cao
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Luxi Cao
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Tingting Zhu
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Tingting Zhu
- Key Laboratory of Nephropathy, Hangzhou, China
- Tingting Zhu
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Tingting Zhu
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Tingting Zhu
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Xiabing Lang
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Xiabing Lang
- Key Laboratory of Nephropathy, Hangzhou, China
- Xiabing Lang
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Xiabing Lang
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Xiabing Lang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Sha Jia
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Sha Jia
- Key Laboratory of Nephropathy, Hangzhou, China
- Sha Jia
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Sha Jia
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Sha Jia
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Yi Yang
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Yi Yang
- Key Laboratory of Nephropathy, Hangzhou, China
- Yi Yang
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Yi Yang
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Yi Yang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Chaohong Zhu
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Chaohong Zhu
- Key Laboratory of Nephropathy, Hangzhou, China
- Chaohong Zhu
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Chaohong Zhu
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Chaohong Zhu
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Yucheng Wang
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Yucheng Wang
- Key Laboratory of Nephropathy, Hangzhou, China
- Yucheng Wang
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Yucheng Wang
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Yucheng Wang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Shi Feng
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Shi Feng
- Key Laboratory of Nephropathy, Hangzhou, China
- Shi Feng
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Shi Feng
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Shi Feng
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Cuili Wang
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Cuili Wang
- Key Laboratory of Nephropathy, Hangzhou, China
- Cuili Wang
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Cuili Wang
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Cuili Wang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Ping Zhang
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Ping Zhang
- Key Laboratory of Nephropathy, Hangzhou, China
- Ping Zhang
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Ping Zhang
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Ping Zhang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Jianghua Chen
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Jianghua Chen
- Key Laboratory of Nephropathy, Hangzhou, China
- Jianghua Chen
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Jianghua Chen
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Jianghua Chen
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Hong Jiang
- Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
- Hong Jiang
- Key Laboratory of Nephropathy, Hangzhou, China
- Hong Jiang
- Kidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, China
- Hong Jiang
- Key Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, China
- Hong Jiang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2020.01360
- Journal volume & issue
-
Vol. 11
Abstract
Organ dysfunction caused by sepsis is life-threatening and results in high mortality. Therapeutic options for sepsis are limited. Pathogenic factors are considered as components of environmental pressure that modify DNA methylation patterns thereby enhancing disease progression. Here, we found that sepsis patients exhibited higher levels of genomic DNA methylation patterns and hypermethylated genes associated with the NF-kB signaling pathway. Therefore, we hypothesized that a DNA methyl transferase inhibitor, Decitabine, may mitigate inflammation and improve survival by inhibiting the NF-κB signaling pathway. To test the hypothesis, mice challenged with caecal ligation and puncture (CLP) were subcutaneously injected with Decitabine solution (0.5, 1, and 1.5 mg/kg) 2 h following operation. Our results indicated that Decitabine reduces DNA methyltransferases (DNMTs), attenuates NF-κB activation, downregulates inflammatory cytokine levels, and inhibits the progression of sepsis. Thus, DNA methylation may be indispensable for sepsis and serve as a predicting factor. The use of Decitabine could represent a novel strategy in the treatment of sepsis.
Keywords
