| Autor: |
Fangfang Sun, Irene Abreu-Rodriguez, Shuang Ye, Steffen Gay, Oliver Distler, Michel Neidhart, Emmanuel Karouzakis |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 14, Iss 6, p e0218551 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0218551 |
| Popis: |
Activation of macrophages and overexpression of TNFα is associated with the pathogenesis of chronic inflammatory diseases. However, the mechanisms leading to TNFα overexpression are still unknown. 5-methylocytosine (5-mC) is an epigenetic modification that is associated with silenced genes. Recent studies showed that it is converted to 5-hydroxylmethylocytosine (5-hmC) and reactivates gene expression through the action of the family of Ten-Eleven-Translocation (TET1-3) enzymes. In this study, we show that 5-hmC levels are increased globally and specifically in the TNFα promoter during the differentiation of monocytes to macrophages. In addition, the levels of 5-hmC are increased upon LPS stimulation of macrophages. Furthermore, CRIPSR stable knockout of TET1 decreases the expression of TNFα and other pro-inflammatory cytokines. In conclusion, we showed that TET1 contributes to the activation of macrophages possibly through regulation of 5-hydroxymethylation in the promoter of pro-inflammatory cytokine genes. The TET1 enzyme could be a promising therapeutic target to inhibit the persistent inflammation caused by macrophages in chronic inflammatory diseases. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
