WFRF:(Thorlacius Henrik)
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- Hawez, AvinLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital (author)
MiR-155 regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis
- Article/chapterEnglish2022
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- 2022
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- LIBRIS-ID:oai:lup.lub.lu.se:4a2be506-5e54-4041-9c6f-dff7e19fb7fe
- https://lup.lub.lu.se/record/4a2be506-5e54-4041-9c6f-dff7e19fb7feURI
- https://doi.org/10.1002/JLB.3A1220-789RRDOI
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- Language:English
- Summary in:English
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- 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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- Taha, DlerLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)dl0400ta (author)
- Algaber, AnwarLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)an6321al (author)
- Madhi, RaedLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-rma (author)
- Rahman, MilladurLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-mdr (author)
- Thorlacius, HenrikLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kir-hth (author)
- KirurgiForskargrupper vid Lunds universitet (creator_code:org_t)
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- In:Journal of Leukocyte Biology111:2, s. 391-4001938-3673
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