Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01360/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway Frontiers in Immunology DNA methylation sepsis CLP NF-κB pathway DNMTs inflammatory cytokine |
| author_facet |
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 |
| author_sort |
Luxi Cao |
| title |
Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway |
| title_short |
Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway |
| title_full |
Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway |
| title_fullStr |
Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway |
| title_full_unstemmed |
Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway |
| title_sort |
inhibiting dna methylation improves survival in severe sepsis by regulating nf-κb pathway |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2020-07-01 |
| description |
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. |
| topic |
DNA methylation sepsis CLP NF-κB pathway DNMTs inflammatory cytokine |
| url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01360/full |
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doaj-2305df95edcc45d8a08caa50c7ae8fa32020-11-25T03:33:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01360527602Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB PathwayLuxi Cao0Luxi Cao1Luxi Cao2Luxi Cao3Luxi Cao4Tingting Zhu5Tingting Zhu6Tingting Zhu7Tingting Zhu8Tingting Zhu9Xiabing Lang10Xiabing Lang11Xiabing Lang12Xiabing Lang13Xiabing Lang14Sha Jia15Sha Jia16Sha Jia17Sha Jia18Sha Jia19Yi Yang20Yi Yang21Yi Yang22Yi Yang23Yi Yang24Chaohong Zhu25Chaohong Zhu26Chaohong Zhu27Chaohong Zhu28Chaohong Zhu29Yucheng Wang30Yucheng Wang31Yucheng Wang32Yucheng Wang33Yucheng Wang34Shi Feng35Shi Feng36Shi Feng37Shi Feng38Shi Feng39Cuili Wang40Cuili Wang41Cuili Wang42Cuili Wang43Cuili Wang44Ping Zhang45Ping Zhang46Ping Zhang47Ping Zhang48Ping Zhang49Jianghua Chen50Jianghua Chen51Jianghua Chen52Jianghua Chen53Jianghua Chen54Hong Jiang55Hong Jiang56Hong Jiang57Hong Jiang58Hong Jiang59Kidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaKidney Disease Center, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, ChinaKey Laboratory of Nephropathy, Hangzhou, ChinaKidney Disease Immunology Laboratory, The Third-Grade Laboratory, State Administration of Traditional Chinese Medicine of China, Beijing, ChinaKey Laboratory of Multiple Organ Transplantation, Ministry of Health of China, Hangzhou, ChinaInstitute of Nephropathy, Zhejiang University, Hangzhou, ChinaOrgan 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.01360/fullDNA methylationsepsisCLPNF-κB pathwayDNMTsinflammatory cytokine |