MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps
(2019) In Frontiers in Immunology 10.- Abstract
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.... (More)
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.
(Less)
- author
- Hawez, Avin LU ; Al-Haidari, Amr LU ; Madhi, Raed LU ; Rahman, Milladur LU and Thorlacius, Henrik LU
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- histone, inflammation, microRNA, NETosis, neutrophils
- in
- Frontiers in Immunology
- volume
- 10
- article number
- 2462
- publisher
- Frontiers Media S. A.
- external identifiers
-
- pmid:31736940
- scopus:85075114779
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2019.02462
- language
- English
- LU publication?
- yes
- id
- 07b5b15c-912f-4aab-a4ef-cd3765d63ed7
- date added to LUP
- 2019-12-02 14:26:01
- date last changed
- 2024-04-17 00:07:25
@article{07b5b15c-912f-4aab-a4ef-cd3765d63ed7, abstract = {{<p>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.</p>}}, author = {{Hawez, Avin and Al-Haidari, Amr and Madhi, Raed and Rahman, Milladur and Thorlacius, Henrik}}, issn = {{1664-3224}}, keywords = {{histone; inflammation; microRNA; NETosis; neutrophils}}, language = {{eng}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{MiR-155 Regulates PAD4-Dependent Formation of Neutrophil Extracellular Traps}}, url = {{http://dx.doi.org/10.3389/fimmu.2019.02462}}, doi = {{10.3389/fimmu.2019.02462}}, volume = {{10}}, year = {{2019}}, }