MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps
Accumulating data suggest that neutrophil extracellular traps (NETs) exert a key function in several diseases. Peptidylarginine deiminase 4 (PAD4) regulates NET formation via citrullination of histones. The aim of this study was to examine the role of miR-155 in controlling PAD4-dependent generation...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02462/full |
| _version_ | 1811199656596602880 |
|---|---|
| author | Avin Hawez Amr Al-Haidari Raed Madhi Milladur Rahman Henrik Thorlacius |
| author_facet | Avin Hawez Amr Al-Haidari Raed Madhi Milladur Rahman Henrik Thorlacius |
| author_sort | Avin Hawez |
| collection | DOAJ |
| description | Accumulating data suggest that neutrophil extracellular traps (NETs) exert a key function in several diseases. Peptidylarginine deiminase 4 (PAD4) regulates NET formation via citrullination of histones. The aim of this study was to examine the role of miR-155 in controlling PAD4-dependent generation of NETs. Bone marrow neutrophils were stimulated with PMA and MIP-2. Pre-incubation of neutrophils with translational inhibitors (cycloheximide or puromycin) markedly decreased NET formation induced by PMA or MIP-2. Neutrophil transfection with a mimic miR-155 increased PMA-induced PAD4 mRNA expression and NET formation. In contrast, transfection with an antagomiR-155 decreased induction of PAD4 mRNA and NETs in response to PMA challenge. Bioinformatical examination of PAD4 revealed a potential binding site in AU-rich elements at the 3′-UTR region. MiR-155 binding to PAD4 was examined by use of target site blockers and RNA immunoprecipitation, revealing that miR-155 regulation of PAD4 mRNA is mediated via AU-rich elements in the 3′-UTR region. In conclusion, our findings demonstrate that miR-155 positively regulates neutrophil expression of PAD4 and expulsion of extracellular traps. Thus, our novel results indicate that targeting miR-155 might be useful to inhibit exaggerated NET generation in inflammatory diseases. |
| first_indexed | 2024-04-12T01:51:14Z |
| format | Article |
| id | doaj.art-250cbf0f2a9b4bc9bdb7b709554e98dc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T01:51:14Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-250cbf0f2a9b4bc9bdb7b709554e98dc2022-12-22T03:52:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02462482517MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular TrapsAvin HawezAmr Al-HaidariRaed MadhiMilladur RahmanHenrik ThorlaciusAccumulating data suggest that neutrophil extracellular traps (NETs) exert a key function in several diseases. Peptidylarginine deiminase 4 (PAD4) regulates NET formation via citrullination of histones. The aim of this study was to examine the role of miR-155 in controlling PAD4-dependent generation of NETs. Bone marrow neutrophils were stimulated with PMA and MIP-2. Pre-incubation of neutrophils with translational inhibitors (cycloheximide or puromycin) markedly decreased NET formation induced by PMA or MIP-2. Neutrophil transfection with a mimic miR-155 increased PMA-induced PAD4 mRNA expression and NET formation. In contrast, transfection with an antagomiR-155 decreased induction of PAD4 mRNA and NETs in response to PMA challenge. Bioinformatical examination of PAD4 revealed a potential binding site in AU-rich elements at the 3′-UTR region. MiR-155 binding to PAD4 was examined by use of target site blockers and RNA immunoprecipitation, revealing that miR-155 regulation of PAD4 mRNA is mediated via AU-rich elements in the 3′-UTR region. In conclusion, our findings demonstrate that miR-155 positively regulates neutrophil expression of PAD4 and expulsion of extracellular traps. Thus, our novel results indicate that targeting miR-155 might be useful to inhibit exaggerated NET generation in inflammatory diseases.https://www.frontiersin.org/article/10.3389/fimmu.2019.02462/fullmicroRNAhistoneinflammationneutrophilsNETosis |
| spellingShingle | Avin Hawez Amr Al-Haidari Raed Madhi Milladur Rahman Henrik Thorlacius MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps Frontiers in Immunology microRNA histone inflammation neutrophils NETosis |
| title | MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps |
| title_full | MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps |
| title_fullStr | MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps |
| title_full_unstemmed | MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps |
| title_short | MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps |
| title_sort | mir 155 regulates pad4 dependent formation of neutrophil extracellular traps |
| topic | microRNA histone inflammation neutrophils NETosis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02462/full |
| work_keys_str_mv | AT avinhawez mir155regulatespad4dependentformationofneutrophilextracellulartraps AT amralhaidari mir155regulatespad4dependentformationofneutrophilextracellulartraps AT raedmadhi mir155regulatespad4dependentformationofneutrophilextracellulartraps AT milladurrahman mir155regulatespad4dependentformationofneutrophilextracellulartraps AT henrikthorlacius mir155regulatespad4dependentformationofneutrophilextracellulartraps |