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MiR-155 regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis

Hawez, Avin LU orcid ; Taha, Dler LU ; Algaber, Anwar LU ; Madhi, Raed LU ; Rahman, Milladur LU orcid and Thorlacius, Henrik LU (2022) In Journal of Leukocyte Biology 111(2). p.391-400
Abstract

Neutrophil extracellular traps (NETs)-mediated tissue damage is a hallmark in abdominal sepsis. Under certain conditions, microRNAs (miRs) can regulate protein expression and cellular functions. The aim of this study was to investigate the role of miR-155 in sepsis-induced NET formation, lung inflammation, and tissue damage. Abdominal sepsis was induced in wild-type (WT) C57BL/6 and miR-155 gene-deficient mice by cecal ligation and puncture (CLP). The amount of DNA-histone complex formation as well as myeloperoxidase (MPO) and citrullinated histone 3 in neutrophils isolated from bone marrow were examined by ELISA and flow cytometry. NETs were detected by electron microscopy in the septic lung. Levels of PAD4 and citrullinated histone 3... (More)

Neutrophil extracellular traps (NETs)-mediated tissue damage is a hallmark in abdominal sepsis. Under certain conditions, microRNAs (miRs) can regulate protein expression and cellular functions. The aim of this study was to investigate the role of miR-155 in sepsis-induced NET formation, lung inflammation, and tissue damage. Abdominal sepsis was induced in wild-type (WT) C57BL/6 and miR-155 gene-deficient mice by cecal ligation and puncture (CLP). The amount of DNA-histone complex formation as well as myeloperoxidase (MPO) and citrullinated histone 3 in neutrophils isolated from bone marrow were examined by ELISA and flow cytometry. NETs were detected by electron microscopy in the septic lung. Levels of PAD4 and citrullinated histone 3 were determined by Western blot in the blood neutrophils. Lung levels of MPO, CXC chemokines, and plasma levels of DNA-histone complexes and CXC chemokines were quantified. In vitro studies revealed that neutrophils from miR-155 gene-deficient mice had less NETs forming ability than WT neutrophils. In the miR-155 gene-deficient mice, CLP yielded much less NETs in the lung tissue compared with WT control. CLP-induced PAD4 levels, histone 3 citrullination, edema, MPO activity, and neutrophil recruitment in the lung were markedly reduced in the mice lacking miR-155. Furthermore, tissue and plasma levels of CXCL1 and CXCL2 were significantly lower in the miR-155 gene-deficient mice compared with WT after induction of abdominal sepsis. Taken together, our findings suggest that miR-155 regulates pulmonary formation of NETs in abdominal sepsis via PAD4 up-regulation and histone 3 citrullination. Thus, targeting miR-155 could be a useful target to reduce pulmonary damage in abdominal sepsis.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Leukocyte Biology
volume
111
issue
2
pages
391 - 400
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85107566844
  • pmid:34114683
ISSN
1938-3673
DOI
10.1002/JLB.3A1220-789RR
language
English
LU publication?
yes
id
4a2be506-5e54-4041-9c6f-dff7e19fb7fe
date added to LUP
2021-06-21 15:19:05
date last changed
2024-04-20 07:47:12
@article{4a2be506-5e54-4041-9c6f-dff7e19fb7fe,
  abstract     = {{<p>Neutrophil extracellular traps (NETs)-mediated tissue damage is a hallmark in abdominal sepsis. Under certain conditions, microRNAs (miRs) can regulate protein expression and cellular functions. The aim of this study was to investigate the role of miR-155 in sepsis-induced NET formation, lung inflammation, and tissue damage. Abdominal sepsis was induced in wild-type (WT) C57BL/6 and miR-155 gene-deficient mice by cecal ligation and puncture (CLP). The amount of DNA-histone complex formation as well as myeloperoxidase (MPO) and citrullinated histone 3 in neutrophils isolated from bone marrow were examined by ELISA and flow cytometry. NETs were detected by electron microscopy in the septic lung. Levels of PAD4 and citrullinated histone 3 were determined by Western blot in the blood neutrophils. Lung levels of MPO, CXC chemokines, and plasma levels of DNA-histone complexes and CXC chemokines were quantified. In vitro studies revealed that neutrophils from miR-155 gene-deficient mice had less NETs forming ability than WT neutrophils. In the miR-155 gene-deficient mice, CLP yielded much less NETs in the lung tissue compared with WT control. CLP-induced PAD4 levels, histone 3 citrullination, edema, MPO activity, and neutrophil recruitment in the lung were markedly reduced in the mice lacking miR-155. Furthermore, tissue and plasma levels of CXCL1 and CXCL2 were significantly lower in the miR-155 gene-deficient mice compared with WT after induction of abdominal sepsis. Taken together, our findings suggest that miR-155 regulates pulmonary formation of NETs in abdominal sepsis via PAD4 up-regulation and histone 3 citrullination. Thus, targeting miR-155 could be a useful target to reduce pulmonary damage in abdominal sepsis.</p>}},
  author       = {{Hawez, Avin and Taha, Dler and Algaber, Anwar and Madhi, Raed and Rahman, Milladur and Thorlacius, Henrik}},
  issn         = {{1938-3673}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{391--400}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Leukocyte Biology}},
  title        = {{MiR-155 regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis}},
  url          = {{http://dx.doi.org/10.1002/JLB.3A1220-789RR}},
  doi          = {{10.1002/JLB.3A1220-789RR}},
  volume       = {{111}},
  year         = {{2022}},
}